Aminolipid compounds, methods for preparing same, and uses thereof

Abstract

The present invention further relates to lipid nanoparticles and pharmaceutical compositions containing the amino lipid compounds, and uses thereof.

Description

[Technical Field]

[0001] The present disclosure relates to amino lipid compounds, methods for preparing the same, and uses thereof. The present disclosure also relates to lipid nanoparticles and pharmaceutical compositions containing the amino lipid compounds, and uses thereof. [Background technology]

[0002] Gene therapy aims to introduce exogenous normal genes into target cells for therapeutic purposes or to induce immune responses. However, gene therapy faces several challenges. In particular, in the case of nucleic acid drugs, it is extremely difficult to directly introduce nucleic acids into cells, and nucleic acid drugs are highly susceptible to degradation by nucleases in the cytoplasm. Delivery of nucleic acid drugs using lipid nanoparticles is widely used. However, the targeting, safety, and delivery efficiency of nucleic acid drug delivery systems need to be further improved. Lipid nanoparticles with different properties must be appropriately selected for different nucleic acid drugs, cells (or tissues, organs), and application scenarios. Therefore, developing different lipid nanoparticles, especially amino lipid compounds used in the production of lipid nanoparticles, as well as related manufacturing methods and applications, is of great research significance and is in high practical demand, especially to meet the delivery needs of nucleic acid drugs 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, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 ,A1,A2,A3,A4,A5,A6,A7,A8,A9,A 10 , X, R1, R2, and R3 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 of treating a disease or disorder in a mammal in need thereof with 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 pharmaceutical for nucleic acid transfer. [Brief explanation of the drawings]

[0005] [Figure 1] 1A-1B show the results of in vivo delivery of lipid nanoparticles containing different amino lipid compounds. [Figure 2] 2A-2B show the results of in vivo safety (ALT enzyme activity) testing of lipid nanoparticles containing different amino lipid compounds. [Figure 3] 3A-3B show the results of in vivo safety (AST enzyme activity) testing of lipid nanoparticles containing different amino lipid compounds. [Figure 4] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations within the spleen. [Figure 5] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations within the spleen. [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 within the spleen. [Figure 8] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations within the spleen. [Figure 9] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations within the spleen. [Figure 10] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations within the spleen. [Figure 11] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations within the spleen. 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 24 hydrocarbyl), 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 10Examples of 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 in the definition of "optionally substituted" below. 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 10Examples 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 stated otherwise 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 24 alkenyl), 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 10Examples 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 16Alkynyl, C2-C 12 Alkynyl, C2-C 10 Examples 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 preferred 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 a monocyclic or polycyclic ring system containing one or more rings composed of 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) 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 a specified number of carbon atoms and at least one heteroatom. A heteroatom refers to an atom other than carbon or hydrogen. In certain embodiments, a heterohydrocarbyl group contains one, two, three, or more heteroatoms. In certain embodiments, a heterohydrocarbyl group contains one or more (e.g., two or three) identical heteroatoms or multiple (e.g., two or three) different heteroatoms. Preferably, the heteroatom is selected from O, N, and S. Examples of heterohydrocarbyl groups include, but are not limited to, -CH2-CH2-O-CH3, -CH2-CH2-CH2-O-CH2-CH3, -CH2-(CH2)3-O-(CH2)5-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2, -CH=CH-O-CH3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, and -CH2-NH-OCH3. Unless stated otherwise explicitly in the specification, a heterohydrocarbyl group or subgroup thereof (e.g., heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, etc.) is 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 "carbocyclyl ring" or "carbocyclyl ring group" refers to an optionally substituted monocyclic or polycyclic structure containing one or more rings of carbon atoms. The ring may be 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, 18-, 19-, or 20-membered. The designation "C3-6 carbocyclyl ring" refers to a carbocyclyl ring containing a single ring having 3 to 6 carbon atoms. The carbocyclyl ring may contain one or more carbon-carbon double or triple bonds and may be either a non-aromatic or aromatic ring (e.g., cycloalkyl or aryl). Examples of carbocyclyl rings include cyclopropyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, and 1,2-dihydronaphthyl. A "carbocyclyl ring" or "carbocyclyl ring group" 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 this specification, a carbocyclyl ring or carbocyclyl ring group is optionally substituted.

[0021] 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 heterocyclic ring, 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 heterocyclic ring, 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 heterocyclic ring, wherein the ring-forming atoms contain 1, 2, or 3 heteroatoms selected from N, O, and S. The heterocyclic ring can contain one or more double or triple bonds and can be a non-aromatic or aromatic ring (e.g., a heterocyclic alkyl or heteroaryl). Examples of heterocycles include, but are not limited to, azetidine, oxetanyl, tetrahydrofuran, pyrrolidine, imidazolidine, pyrazolidine, tetrahydropyran, piperidine, morpholine, thiomorpholine, piperazine, preferably pyrrolidine, piperidine, piperazine, morpholine.Heterocycles may be optionally substituted with one or more substituents, and for substituents, the definition of "optionally substituted" is referred to below.Unless otherwise expressly stated herein, heterocycles, heterocyclyls, or heterocyclylenes are optionally substituted.

[0022] 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.

[0023] 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.

[0024] 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, CN, -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 alkyl 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 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 Furthermore, halogens such as -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, CN, 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.

[0025] 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)Xi, where Xi 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 groups (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., -NR, -N(R)H, or -NH), carbamoyl (e.g., -OC(=O)NR, -OC(=O)N(R)H, or or -OC(=O)NH), sulfonamide groups (e.g., -S(=O)NR, -S(=O)NRH, -S(=O)NH, -N(R)S(=O)R, -N(H)S(=O)R, -N(R)S(=O)H, or -N(H)S(=O)H), alkyl, alkenyl, alkynyl, cyclohydrocarbyl (e.g., cycloalkyl, cycloalkenyl, or cycloalkynyl), heterocyclohydrocarbyl (e.g., heterocycloalkyl containing one or more heteroatoms selected from S, N, and O), , 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(Riii), -OC(=O)N(Riii), -CH(NRii) i)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(O Riii) C(=O)ORiii, -N(ORiii)C(=O)N(Riii)2, -N(ORiii)C(=S)N(Riii)2, -N(ORiii)C(NRiii)(N(Riii)2, -N(ORiii)C(CHRiii)N(Riii)2,In any of the above, R is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, or heteroalkynyl, as defined herein. In some embodiments, R is hydrogen, C-C, as defined herein. 12 Alkyl, or C1-C 12 Alkenyl, or C1-C 12 Alkynyl, or C1-C 12 Heteroalkyl, or C1-C 12 Heteroalkenyl, or C3-C 12 It is heteroalkynyl.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] In certain embodiments, "stereoisomer" also includes E isomers, Z isomers, or mixtures thereof, cis isomers, trans isomers, or mixtures thereof.

[0033] 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]

[0034] During the ceremony: X is C or N; L1, L2, L3, L4, L5, and L6 are each independently a C1-C6 hydrocarbylene or a bond; L7, L8, L9, L 10 , L 11 , and L 12 are independently C1-C 18 is a hydrocarbylene or bond; A1, A2, A3, A4, A5, A6, A7, A8, A9, and A 10are independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC (=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -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 L 13 are independently C1-C8 hydrocarbylene or a bond; R1 and R2 are each independently H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, A 11 R5, or -C(R6)(OL 14 A 12 R7)2; Each A 11 are independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N( R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13-SR4)-, -N(R4)-, -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 benzene ring; Each A 12 are independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N( R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 -SR4)-, -N(R4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(=O)2O-, a benzene ring, or a bond; each R4 is independently H, C1-C6 hydrocarbyl, or C1-C6 heterohydrocarbyl containing O or S; Each R5 is independently H, C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; each R6 is independently H or C1-C6 hydrocarbyl; Each L 14 are independently C1-C 18 is a hydrocarbylene or bond; Each R7 is independently 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; R3 is -L 15 -Z, [ka] and; L 15 is C1-C 12 is a hydrocarbylene or bond; Z is H, a carbocyclyl ring, a heterocyclyl ring, -CN, -OR8, or -OL 16 N(R8)2, -C(=O)R8, -C(=O)SR8, -OC(=O)R8, -OC(=O)OR8, -OL 16 OR8, -N(R8)2, -C(=O)N(R8)2, -C(=S)N(R8)2, -S(=O)2R8, -S(=O)2N(R8)2 , -OC(=O)N(R8)2, -C(NR8)N(R8)2, -C(NR8)R8, -C(=O)N(R8)OR8, -CH(R8)N (R8)C(=O)OR8, -C(R8)3, -N(R8)C(=O)R8, -N(R8)C(=O)OR8, -N(R8)S(=O)2 R8, -N(R8)C(=O)N(R8)2, -N(R8)C(=S)N(R8)2, -N(R8)C(NR8)N(R8)2, -N(R 8)C(CHR8)N(R8)2, -N(OR8)C(=O)R8, -N(OR8)S(=O)2R8, -N(OR8)C(=O)OR8, -N(OR8)C(=O)N(R8)2, -N(OR8)C(=S)N(R8)2, -N(OR8)C(NR8)N(R8)2, -N( OR8)C(CHR8)N(R8)2, -OP(=O)(OR8)2, -P(=O)(OR8)2, -C(=N-CN)N(R8)2, -C(=NO-CH3)N(R8)2, -C(=N-SO2-NH2)N(R8)2, or -C(=CH-NO2)N(R8)2; Each R8 is independently hydrogen, C1-C 12 Alkyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C containing one, two, three or more double bonds and S or O 12 Heteroalkenyl or C2-C containing one, two, three or more triple bonds and S or O 12is heteroalkynyl, and Each L 16 are independently C1-C 18 It is a hydrocarbylene or bond.

[0035] In some embodiments, the present disclosure provides: Z is [ka] (In the formula: Y1 and Y2 are each independently O or S; Each R9 is independently H, halogen, -R b , -N(R b )2, Cyano, -N3, -C(=O)OR b , -OC(=O)R b , -OR b , -SR b , -S(-O)R b , -S(=O)OR b , -S(=O)2OR b , -N(R b )2, -N(R b )S(=O)2R b , -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R a OR b )2; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C containing one, two, three or more double bonds and S or O12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and S or O 12 heteroalkynylene, Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C containing one, two, three or more double bonds and S or O 12 Heteroalkenyl or C2-C containing one, two, three or more triple bonds and S or O 12 and R is a heteroalkynyl.), or a pharmaceutically acceptable salt thereof.

[0036] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I) above, or a pharmaceutically acceptable salt thereof, wherein Z is any of the following: [ka] [ka] [ka]

[0037] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I) above, or a pharmaceutically acceptable salt thereof, wherein R3 is any of the following: [ka] [ka] wherein a is 0, 1, 2, 3, 4, or 5; and each R 10 are independently H or C-C hydrocarbyl, preferably C-C hydrocarbyl. In some embodiments, each is independently C, C, or C alkyl, or C or C alkenyl, or C or C alkynyl.

[0038] In some embodiments, the present disclosure provides L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , L 13 , L 14 , L 15 , and L 16 are each independently substituted with hydroxyl, halogen, alkyl, alkenyl, alkynyl, cyano, oxygen, sulfur, nitrogen, an ester group, aryl, cycloalkyl, cycloalkenyl, amido, alkoxy, or alkylthio, or a pharmaceutically acceptable salt thereof.

[0039] In some embodiments, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , L 13 , L 14 , L 15 , and L 16 are each independently hydroxyl, halogen, O, S, N, cyano, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -R a OC(=O)Rb , or -R a SR b is replaced by; L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , L 13 , L 14 , L 15 , and L 16 However, each independently, -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -R a OC(=O)R b , or -R a SR b When substituted with R a and / or R b are L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , L 13 , L 14 , L 15 , or L 16 may be linked to a C atom of to form a 3-, 4-, 5-, or 6-membered ring; During the ceremony: Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C containing one, two, three or more double bonds and S or O12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and S or O 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C containing one, two, three or more double bonds and S or O 12 Heteroalkenyl or C2-C containing one, two, three or more triple bonds and S or O 12 It is heteroalkynyl.

[0040] In another aspect, the present disclosure provides an amino lipid compound represented by the following formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: [ka] During the ceremony: X is C, N, or CR 13 and; L1, L2, L3, L4, L5, and L6 are each independently C1-C6 hydrocarbylene, a C3-C8 carbocyclyl ring, a heterocyclyl ring, C1-C6 heterohydrocarbylene, or a bond; L7, L8, L9, L 10 , L 11 , and L 12 are independently C1-C 18 Hydrocarbylene, C1-C 18 heterohydrocarbylene, or a bond; A1, A2, A3, A4, A5, A6, A7, A8, A9, and A 10are independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC (=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] or is a bond; Each L 13 are independently C1-C8 hydrocarbylene, C1-C8 heterohydrocarbylene, or a bond; R1 and R2 are each independently H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, A 11 R5, -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7); Each A 11are independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N( R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 -SR4)-, -N(R4)-, -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 benzene ring; Each A 12 are independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N( R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 -SR4)-, -N(R4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(=O)2O-, a benzene ring, or a bond; each R4 is independently H, C1-C6 hydrocarbyl, or C1-C6 heterohydrocarbyl; Each R5 is independently H, C1-C 24 Hydrocarbyl, or C1-C 24is heterohydrocarbyl; each R6 is independently H, C1-C6 hydrocarbyl, or C1-C6 heterohydrocarbyl; Each L 14 are independently C1-C 18 Hydrocarbylene, C1-C 18 heterohydrocarbylene, or a bond; Each R7 is independently 24 Hydrocarbyl or C1-C 24 is heterohydrocarbyl; R3 is -L 15 -Z; L 15 is C1-C 12 Hydrocarbylene, C1-C 12 heterohydrocarbylene, or a bond; Z is H, a carbocyclyl ring, a heterocyclyl ring, -CN, -OR8, or -OL 16 N(R8)2, -C(=O)OR8, -C(=O)R8, -C(=O)SR8, -OC(=O)R8, -OC(=O)OR8, -OL 16OR8, -N(R8)2, -C(=O)N(R8)2, -C(=S)N(R8)2, -S(=O)2R8, -S(=O)2N(R8)2, -OC(=O)N(R8)2, -C(=NR8)N(R8)2, -C(=NR8)R8, -C(=O)N(R8)OR8, -CH(R8)N (R8)C(=O)OR8, -C(R8)3, -N(R8)C(=O)R8, -N(R8)C(=O)OR8, -N(R8)S(=O)2R 8, -N(R8)C(=O)N(R8)2, -N(R8)C(=S)N(R8)2, -N(R8)C(=NR8)N(R8)2, -N(R8 )C(=CHR8)N(R8)2, -N(OR8)C(=O)R8, -N(OR8)S(=O)2R8, -N(OR8)C(=O)OR8, -N(OR8)C(=O)N(R8)2, -N(OR8)C(=S)N(R8)2, -N(OR8)C(NR8)N(R8)2, -N(O R8)C(=CHR8)N(R8)2, -OP(=O)(OR8)2, -P(=O)(OR8)2, -C(=N-CN)N(R8)2, -C(=NO-CH3)N(R8)2, -C(=N-SO2-NH2)N(R8)2, -C(=CH-NO2)N(R8)2, -C(=O)OR 11 , -N(R8)R 11 , -N(R8)S(=O)2R 11 , -N(R8)C(=NR 12 )N(R8)2, -N(R8)C(=CHR 12 )N(R8)2, -N(OR8)C(=NR 12 )N(R8)2, -N(OR8)C(=CHR 12 )N(R8)2, -C(=NR 12 )N(R8)2, -C(=NR 12 )R8, or -C(R8)N(R8)2C(=O)OR8; Each R8 is independently hydrogen or C1-C 12 Alkyl or C2-C containing one, two, three or more double bonds 12 Alkenyl or C2-C containing one, two, three or more triple bonds 12 Alkynyl, or C1-C 12 Heteroalkyl or C2-C containing one, two, three or more double bonds 12Heteroalkenyl or C2-C containing one, two, three or more triple bonds 12 is heteroalkynyl; Each R 11 independently, C 3-6 is a carbocyclyl or heterocyclyl ring; Each R 12 are independently H, CN, NO2, C 1-6 Alkyl, -OR, -S(O)2R, -S(O)2N(R)2, C 2-6 Alkenyl, C 3-6 is a carbocyclyl or heterocyclyl ring; Each L 16 are independently C1-C 18 Hydrocarbylene, C1-C 18 heterohydrocarbylene, or a bond; R 13 is H, C1-C6 hydrocarbyl, or C1-C6 heterohydrocarbyl.

[0041] The present disclosure provides amino lipid compounds represented by formula (IA) above, or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprising one or more of the following features, where applicable:

[0042] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L1, L2, L3, L4, L5, and L6 are each independently C1, C2, C3, C4, C5, or C6 hydrocarbylene, or C1, C2, C3, C4, C5, or C6 heterohydrocarbylene.

[0043] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L1 is C1-C6 alkylene, or C1-C6 heteroalkylene containing O, N, or S, or a bond. In some embodiments, L1 is C4, C5, or C6 alkylene. In some embodiments, L1 is C1, C2, C3, or C4 alkylene. In some embodiments, L1 is C1-C3 alkylene. In some other embodiments, L1 is C4 alkylene. In some embodiments, L1 is a bond.

[0044] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L2 is C1-C6 alkylene, or C1-C6 heteroalkylene containing O, N, or S, or a bond. In some embodiments, L2 is C5 or C6 alkylene. In some embodiments, L2 is C1, C2, C3, or C4 alkylene. In some embodiments, L2 is a bond.

[0045] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L3 is C1-C6 alkylene, or C1-C6 heteroalkylene containing O, N, or S, or a bond. In some embodiments, L3 is a C4, C5, or C6 alkylene. In some embodiments, L3 is C2 or C3 alkylene. In some embodiments, L3 is C1 alkylene, or a bond.

[0046] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L4 is a bond. In some embodiments, L4 is C4, C5, or C6 alkylene, or C4, C5, or C6 heteroalkylene containing O, N, or S. In some embodiments, L4 is a C2 or C3 alkylene or a C2 or C3 heteroalkylene containing O, N, or S. In some embodiments, L4 is C1 alkylene, or C1 heteroalkylene containing O, N, or S, or a bond. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L5 is a bond.

[0047] In some embodiments, L5 is C4, C5, or C6 alkylene, or C4, C5, or C6 heteroalkylene containing O, N, or S. In some embodiments, L5 is C2 or C3 alkylene, or C2 or C3 heteroalkylene containing O, N, or S. In some embodiments, L5 is C1 alkylene, or C1 heteroalkylene containing O, N, or S, or a bond.

[0048] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L6 is a bond. In some embodiments, L6 is C4, C5, or C6 alkylene, or C4, C5, or C6 heteroalkylene containing O, N, or S. In some embodiments, L6 is C2 or C3 alkylene, or C2 or C3 heteroalkylene containing O, N, or S. In some embodiments, L6 is C1 alkylene, or C1 heteroalkylene containing O, N, or S, or a bond.

[0049] In some embodiments, the present disclosure provides L7, L8, L9, L 10 , L 11 , and L 12 However, 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 Hydrocarbylene, 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 (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbylene.

[0050] In some embodiments, the present disclosure provides a method for treating a cancer cell comprising administering to a patient a cancer treatment agent comprising: 18 Alkylene, or C1-C 18 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: In some embodiments, L7 is C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 heteroalkylene, or a bond.

[0051] In some embodiments, L7 is C1-C 14 It is alkylene. In some embodiments, L7 is C4-C11 It is alkylene. In some embodiments, L7 is a C2 or C3 alkylene. In some embodiments, L7 is C6-C9 alkylene. In some embodiments, L7 is C7 or C8 alkylene. In some embodiments, L7 is C1-C4 alkylene. In some embodiments, L7 is a bond.

[0052] In some embodiments, the present disclosure provides a method for treating a cancer cell comprising administering to a patient a cancer treatment agent comprising: 18 Alkylene, or C1-C 18 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: In some embodiments, L8 is C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 heteroalkylene, or a bond. In some embodiments, L8 is C1-C 14 It is alkylene. In some embodiments, L8 is C4-C 11 It is alkylene. In some embodiments, L8 is C2 or C3 alkylene. In some embodiments, L8 is C6-C9 alkylene. In some embodiments, L8 is C7 or C8 alkylene. In some embodiments, L8 is C1-C4 alkylene. In some embodiments, L8 is a bond.

[0053] In some embodiments, the present disclosure provides a method for treating a cancer cell comprising administering to a patient a cancer treatment agent comprising: 18 Alkylene, or C1-C 18 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: In some embodiments, L9 is C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 heteroalkylene, or a bond. In some embodiments, L9 is C1-C 14 It is alkylene. In some embodiments, L9 is C1-C8 alkylene. In some embodiments, L9 is C3-C6 alkylene. In some embodiments, L9 is C2 alkylene. In some embodiments, L9 is C3 alkylene. In some embodiments, L9 is C5 or C6 alkylene. In some embodiments, L9 is a bond.

[0054] In some embodiments, the present disclosure provides L 10 C1-C 18 Alkylene, or C1-C 18The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: In some embodiments, L 10 are C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 heteroalkylene, or a bond. In some embodiments, L 10 is C1-C 14 It is alkylene. In some embodiments, L 10 is C1-C8 alkylene. In some embodiments, L 10 is a C3-C6 alkylene. In some embodiments, L 10 is a C2 alkylene. In some embodiments, L 10 is a C3 alkylene. In some embodiments, L 10 is a C5 or C6 alkylene. In some embodiments, L 10 is a bond.

[0055] In some embodiments, the present disclosure provides L 11 C1-C 18 Alkylene, or C1-C 18 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: In some embodiments, L 11 are C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 heteroalkylene, or a bond. In some embodiments, L 11 is C1-C 14 It is alkylene. In some embodiments, L 11 is C1-C8 alkylene. In some embodiments, L 11 is a C2 alkylene. In some embodiments, L 11 is a C3-C6 alkylene. In some embodiments, L 11 is a C3 alkylene. In some embodiments, L 11 is a C5 or C6 alkylene. In some embodiments, L 11 is a bond.

[0056] In some embodiments, the present disclosure provides L 12 C1-C 18 Alkylene, or C1-C 18 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: In some embodiments, L 12 are C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C12 , C 13 , C 14 , C 15 , or C 16 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 heteroalkylene, or a bond. In some embodiments, L 12 is C1-C 14 It is alkylene. In some embodiments, L 12 is C1-C8 alkylene. In some embodiments, L 12 is a C2 alkylene. In some embodiments, L 12 is a C3-C6 alkylene. In some embodiments, L 12 is a C3 alkylene. In some embodiments, L 12 is a C5 or C6 alkylene. In some embodiments, L 12 is a bond.

[0057] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1, A2, A3, A4, A5, or A6 is each independently -N(R4)-. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R4 is independently C1, C2, C3, C4, C5, or C6 hydrocarbyl, or C1, C2, C3, C4, C5, or C6 heterohydrocarbyl.

[0058] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R4 is independently C1, C2, C3, C4, C5, or C6 alkyl, or C1, C2, C3, C4, C5, or C6 heteroalkyl containing O, N, or S. In some embodiments, each R4 is independently a straight-chain C1, C2, C3, C4, C5, or C6 alkyl, or a straight-chain C1, C2, C3, C4, C5, or C6 heteroalkyl containing O, N, or S.

[0059] In some embodiments, each R4 is independently a branched C3, C4, C5, or C6 alkyl or a branched C3, C4, C5, or C6 heteroalkyl containing O, N, or S. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R4 is independently a C2, C3, C4, C5, or C6 alkenyl containing one, two, or more double bonds, or a C2, C3, C4, C5, or C6 heteroalkenyl containing one, two, or more double bonds and O, N, or S.

[0060] In some embodiments, each R4 is independently a straight-chain C2, C3, C4, C5, or C6 alkenyl containing one, two, or more double bonds, or a straight-chain C2, C3, C4, C5, or C6 heteroalkenyl containing one, two, or more double bonds and O, N, or S. In some embodiments, each R4 is independently a branched C3, C4, C5, or C6 alkenyl containing one, two, or more double bonds, or a branched C3, C4, C5, or C6 heteroalkenyl containing one, two, or more double bonds and O, N, or S.

[0061] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R4 is independently a C2, C3, C4, C5, or C6 alkynyl containing one, two, or more triple bonds, or a C2, C3, C4, C5, or C6 heteroalkynyl containing one, two, or more double bonds and O, N, or S.

[0062] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R4 may be independently linked to a C atom of L1, L2, L3, L4, L5, or L6 to form a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered mono- or polycyclic N-atom-containing heterocyclyl ring.

[0063] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R4 is independently H, or C1, C2, C3, C4, C5, or C6 alkyl. In some embodiments, each R4 is independently H. In some embodiments, each R4 is independently C1 or C2 alkyl. In some embodiments, each R4 is independently C3 or C4 alkyl. In some embodiments, each R4 is independently a C5 or C6 alkyl.

[0064] In some embodiments, the present disclosure provides A1, A2, A3, A4, A5, A6, A7, A8, A9, and A 10are independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC (=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0065] In some embodiments, A1, A2, A3, A4, A5, A6, A7, A8, A9, and A 10 are independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C (=O)O-, -N(R4)C(=O)N(R4)-, -N(C(=O)R4), -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] is.

[0066] In some embodiments, the present disclosure provides a method for the preparation of aryl arylsulfates, wherein at least three, e.g., 3, 4, 5, or 6, of A1, A2, A3, A4, A5, and A6 are each independently selected from the group consisting of -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0067] In some embodiments, the present disclosure provides that each L 13 are independently C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbylene, or C1, C2, C3, C4, C5, C6, C7, or C8 heterohydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, the present disclosure provides that each L 13are independently C1, C2, C3, C4, C5, C6, C7, or C8 alkylene, or C1, C2, C3, C4, C5, C6, C7, or C8 heteroalkylene containing O, N, or S, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0068] In some embodiments, each L 13 are independently a straight chain C1, C2, C3, C4, C5, C6, C7, or C8 alkylene or a straight chain C1, C2, C3, C4, C5, C6, C7, or C8 heteroalkylene containing O, N, or S. In some embodiments, each L 13 is independently a branched C3, C4, C5, C6, C7, or C8 alkylene, or a branched C3, C4, C5, C6, C7, or C8 heteroalkylene containing O, N, or S. In some embodiments, the present disclosure provides that each L 13 are independently a C2, C3, C4, C5, C6, C7, or C8 alkenylene containing one, two, or more double bonds, or a C2, C3, C4, C5, C6, C7, or C8 heteroalkenylene containing one, two, or more double bonds and O, N, or S, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, each L 13 is independently a straight-chain C2, C3, C4, C5, C6, C7, or C8 alkenylene containing one, two, or more double bonds, or a straight-chain C2, C3, C4, C5, C6, C7, or C8 heteroalkenylene containing one, two, or more double bonds and O, N, or S.

[0069] In some embodiments, each L 13is independently a branched C3, C4, C5, C6, C7, or C8 alkenylene containing one, two, or more double bonds, or a branched C3, C4, C5, C6, C7, or C8 heteroalkenylene containing one, two, or more double bonds and O, N, or S. In some embodiments, the present disclosure provides that each L 13 are independently a C2, C3, C4, C5, C6, C7, or C8 alkynylene containing one, two, or more triple bonds, or a C2, C3, C4, C5, C6, C7, or C8 heteroalkynylene containing one, two, or more triple bonds and O, N, or S, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, each L 13 are independently a straight-chain C2, C3, C4, C5, C6, C7, or C8 alkynylene containing one, two, or more triple bonds, or a straight-chain C2, C3, C4, C5, C6, C7, or C8 heteroalkynylene containing one, two, or more triple bonds and O, N, or S. In some embodiments, each L 13 is independently a branched C4, C5, C6, C7, or C8 alkynylene containing one, two, or more triple bonds, or a branched C4, C5, C6, C7, or C8 heteroalkynylene containing one, two, or more triple bonds and O, N, or S.

[0070] 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 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbyl. In some embodiments, the present disclosure provides a method for isolating an alkyl group containing aryl groups, wherein R and R are each independently a straight chain C-C 24 Alkyl or straight chain C2-C containing 1, 2, 3, 4 or more double bonds 24 Alkenyl or straight chain C2-C containing 1, 2, 3, 4 or more triple bonds 24 Alkynyl or straight chain C1-C containing O, N, or S 24 Heteroalkyl or straight chain C2-C containing 1, 2, 3, 4 or more double bonds and O, N, or S 24 Heteroalkenyl or straight chain C2-C containing 1, 2, 3, 4 or more triple bonds and O, N, or S 24 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0071] 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 , C19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more double bonds 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, straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more triple bonds 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, 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 containing 1, 2, 3, 4 or more double bonds 10 , C11 , 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 containing 1, 2, 3, 4 or more triple bonds 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 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0072] 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, branched C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more double bonds 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, branched C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more triple bonds 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, branched C3, C4, C5, C6, C7, C8, C9, C containing O, N, 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, branched C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34 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 C24 Heteroalkenyl, branched C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, 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 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0073] In some embodiments, the present disclosure provides that R and R are each independently a straight or 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 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is alkyl. In some embodiments, R and R are each independently a straight or branched C-C 20 It is alkyl. In some embodiments, R and R are each independently a straight or branched C-C 11 It is alkyl. In some embodiments, R and R are each independently a straight or branched C 15 -C 19It is alkyl. In some embodiments, the present disclosure provides a method for treating a cancer cell comprising administering to a patient a cancer-related condition, wherein R and R are each independently selected from the group consisting of: 11 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is R5.

[0074] In some embodiments, the present disclosure provides that each R5 is 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 , 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 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbyl.

[0075] In some embodiments, the present disclosure provides that each R5 is independently a straight chain C1-C 24 Alkyl or straight chain C2-C containing 1, 2, 3, 4 or more double bonds 24 Alkenyl or straight chain C2-C containing 1, 2, 3, 4 or more triple bonds 24 Alkynyl or straight chain C1-C containing O, N, or S24 Heteroalkyl or straight chain C2-C containing 1, 2, 3, 4 or more double bonds and O, N, or S 24 Heteroalkenyl or straight chain C2-C containing 1, 2, 3, 4 or more triple bonds and O, N, or S 24 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0076] In some embodiments, the present disclosure provides that each R5 independently represents a branched C3-C 24 Alkyl or branched C3-C containing 1, 2, 3, 4 or more double bonds 24 Alkenyl or branched C4-C containing 1, 2, 3, 4 or more triple bonds 24 Alkynyl or branched C3-C containing O, N, or S 24 Heteroalkyl or branched C3-C containing 1, 2, 3, 4, or more double bonds and O, N, or S 24 Heteroalkenyl or branched C4-C containing 1, 2, 3, 4, or more triple bonds and O, N, or S 24 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0077] In some embodiments, the present disclosure provides a compound wherein R and R are each independently —C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, the present disclosure provides that R and R are further each independently —C(R)(C(═O)OL 14A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7)R7, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0078] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R1 and R2 are each independently -C(R6)(OR7)2, -C(R6)(SR7)2, -C(R6)(SR7)(OR7), -C(R6)(C(=O)OR7)2, -C(R6)(OC(=O)R7)2, -C(R6)(C(=O)OR7)R7, or -C(R6)(OC(=O)R7)R7. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R6 is independently C1, C2, C3, C4, C5, or C6 hydrocarbyl, or C1, C2, C3, C4, C5, or C6 heterohydrocarbyl.

[0079] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R6 is independently C1, C2, C3, C4, C5, or C6 alkyl, or H. In some embodiments, each R6 is independently C1-C3 alkyl. In some embodiments, each R6 is H.

[0080] In some embodiments, the present disclosure provides that each L 14 are independent, 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 Hydrocarbylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N 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 (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbylene.

[0081] In some embodiments, the present disclosure provides that each L 14 are independent, 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 (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: In some embodiments, each L 14 are independently C1-C 12 alkylene, or a bond. In some embodiments, each L 14 are independently C1-C8 alkylene, or a bond. In some embodiments, each L 14 are independently C1-C4 alkylene, or a bond. In some embodiments, each L 14 are independently C1-C3 alkylene, or a bond.

[0082] In some embodiments, the present disclosure provides that each R is 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 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbyl.

[0083] In some embodiments, the present disclosure provides that each R7 is independently a straight chain C1-C 24 Alkyl or straight chain C2-C containing 1, 2, 3, 4 or more double bonds 24 Alkenyl or straight chain C2-C containing 1, 2, 3, 4 or more triple bonds 24 Alkynyl or straight chain C1-C containing O, N, or S 24 Heteroalkyl or straight chain C2-C containing 1, 2, 3, 4 or more double bonds and O, N, or S 24 Heteroalkenyl or straight chain C2-C containing 1, 2, 3, 4 or more triple bonds and O, N, or S 24Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0084] In some embodiments, the present disclosure provides that each R7 independently represents a 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 Alkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more double bonds 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, straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more triple bonds 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, straight chain 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 Heteroalkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more double bonds 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 containing 1, 2, 3, 4 or more triple bonds 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 (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0085] In some embodiments, the present disclosure provides that each R7 independently represents a branched C3-C 24 Alkyl or branched C3-C containing 1, 2, 3, 4 or more double bonds24 Alkenyl or branched C4-C containing 1, 2, 3, 4 or more triple bonds 24 Alkynyl or branched C3-C containing O, N, or S 24 Heteroalkyl or branched C3-C containing 1, 2, 3, 4, or more double bonds and O, N, or S 24 Heteroalkenyl or branched C4-C containing 1, 2, 3, 4, or more triple bonds and O, N, or S 24 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0086] In some embodiments, the present disclosure provides that each R is independently 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 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl, branched C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more double bonds 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, branched C4, C5, C6, C7, C8, C9, C containing 1, 2, 3, 4 or more triple bonds 10 , C 11 , C 12 , C13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkynyl, branched C3, C4, C5, C6, C7, C8, C9, C containing O, N, 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, branched C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34 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, branched C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, 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 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0087] In some embodiments, each R is independently selected from C, C, C, C, C, C, 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, alkenyl, or alkynyl, or H. In some embodiments, each R7 is independently C1-C4 alkyl, alkenyl, or alkynyl, or H. In some embodiments, each R7 is independently a C2 or C3 alkyl, alkenyl, or alkynyl. In some embodiments, each R7 is independently C5-C 10 It is alkyl, alkenyl, or alkynyl. In some embodiments, each R7 is independently C 11 -C 21 It is alkyl, alkenyl, or alkynyl. In some embodiments, each R7 is independently C 16 -C 18 It is alkyl, alkenyl, or alkynyl.

[0088] In some embodiments, R5 or R7 are each independently: [ka] is selected from.

[0089] In some embodiments, the present disclosure provides that R1 and R2 are each independently: [ka] [ka] The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, selected from:

[0090] In some embodiments, the present disclosure provides L 15 are C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , or C 12 Hydrocarbylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N or S 10 , C 11 , or C 12 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbylene. In some embodiments, the present disclosure provides L 15 is a bond, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, the present disclosure provides L 15 are C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , or C 12 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , or C 12 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heteroalkylene.

[0091] In some embodiments, the present disclosure provides that each R is independently selected from a linear C, ... 10 , C 11 , or C 12 Alkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing 1, 2, 3 or more double bonds 10 , C 11 , or C 12 Alkenyl heteroalkyl, straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing one, two, three or more triple bonds 10 , C 11 , or C 12 Alkynyl heteroalkyl or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32 10 , C 11 , or C 12 Heteroalkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, 10 , C 11 , or C 12 Heteroalkenyl Heteroalkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C3 10 , C 11 , or C 12 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0092] In some embodiments, the present disclosure provides that each R is independently a branched C, ... 10 , C 11 , or C 12 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing one, two, three or more double bonds 10 , C 11 , or C 12Alkenyl heteroalkyl or branched C4, C5, C6, C7, C8, C9, C containing one, two, three or more triple bonds 10 , C 11 , or C 12 Alkynyl heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C 10 , C 11 , or C 12 Heteroalkyl, branched C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34 10 , C 11 , or C 12 Heteroalkenyl Heteroalkyl or branched C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, 10 , C 11 , or C 12 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0093] In some embodiments, the present disclosure provides 11 independently, C 3-6 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the ring is a carbocyclyl ring. In some embodiments, each R 11 is independently C3, C4, C5, or C6 cycloalkyl, or C3, C4, C5, or C6 cycloalkenyl. In some embodiments, each R 11 is independently C3-C6 cycloalkyl, for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0094] In some embodiments, each R 11 are independently -OH, halogen, C 1-6 C optionally substituted with substituents such as alkyl 3-6cycloalkyl; for example, R 11 is cyclohexyl substituted with -OH, for example, 2-hydroxycyclohexyl. In some embodiments, the present disclosure provides 11 are independently a heterocyclyl ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, each R 11 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring. In some embodiments, each R 11 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring containing N, O, or S. In some embodiments, each R 11 is independently a 5- or 6-membered heterocyclyl ring containing N, O, or S.

[0095] In some embodiments, the present disclosure provides 12 is independently C1, C2, C3, C4, C5, or C6 alkyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, the present disclosure provides 12 is independently C2, C3, C4, C5, or C6 alkenyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, the present disclosure provides 12 independently, C 3-6 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the ring is a carbocyclyl ring. In some embodiments, each R 12 is independently C3, C4, C5, or C6 cycloalkyl, or C3, C4, C5, or C6 cycloalkenyl. In some embodiments, each R 12is independently C3-C6 cycloalkyl, for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In some embodiments, each R 12 are independently -OH, halogen, C 1-6 C optionally substituted with substituents such as alkyl 3-6 cycloalkyl; for example, R 12 is cyclohexyl substituted with -OH, for example, 2-hydroxycyclohexyl.

[0096] In some embodiments, the present disclosure provides 12 are independently a heterocyclyl ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, each R 12 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring. In some embodiments, each R 12 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring containing N, O, or S. In some embodiments, each R 12 is independently a 5- or 6-membered heterocyclyl ring containing N, O, or S.

[0097] In some embodiments, the present disclosure provides that each L 16 are independent, 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 Hydrocarbylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N 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 (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbylene. In some embodiments, the present disclosure provides that each L 16 is independently C1, C2, C3, C4, or C5 alkylene. 16 are independently C2-C4 alkylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0098] In some embodiments, the present disclosure provides 3-10 In some embodiments, Z is C. 3-8 A carbocyclyl ring is, for example, a C3 carbocyclyl ring, a C4 carbocyclyl ring, a C5 carbocyclyl ring, a C6 carbocyclyl ring, a C7 carbocyclyl ring, or a C8 carbocyclyl ring.

[0099] In some embodiments, the present disclosure provides a compound in which Z is C optionally substituted with one or more substituents. 3-8 Cycloalkyl, such as cyclopropyl optionally substituted with one or more substituents, cyclobutyl optionally substituted with one or more substituents, cyclopentyl optionally substituted with one or more substituents, cyclohexyl optionally substituted with one or more substituents, cycloheptyl optionally substituted with one or more substituents, and cyclooctyl optionally substituted with one or more substituents, wherein the substituents are hydroxyl, oxygen, amino (—NH), mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12may be independently selected from, but are not limited to, alkoxy, halogen, sulfur (=S), a C3-C8 heterocyclyl ring, or aryl, including the above-mentioned amino, mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the alkoxy, C3-C8 heterocyclyl ring, or aryl may be further substituted.

[0100] In some embodiments, the present disclosure provides a compound in which Z is C optionally substituted with one or more substituents. 3-8 Cycloalkenyl, for example, cyclopropenyl optionally substituted with one or more substituents, cyclobutenyl optionally substituted with one or more substituents, cyclopentenyl optionally substituted with one or more substituents, cyclohexenyl optionally substituted with one or more substituents, cycloheptenyl optionally substituted with one or more substituents, and cyclooctenyl optionally substituted with one or more substituents, wherein the substituents are hydroxyl, oxygen, amino (—NH), mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 may be independently selected from, but are not limited to, alkoxy, halogen, sulfur (=S), a C3-C8 heterocyclyl ring, or aryl, including the above-mentioned amino, mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the alkoxy, C3-C8 heterocyclyl ring, or aryl may be further substituted.

[0101] In some embodiments, Z is cyclobutenyl substituted with one or more of oxygen, amino, and alkylamino, wherein the alkylamino is further substituted with, for example, C-C 12 Substituted with one or more of alkoxy, amino, mono- or di-alkylamino, and halogen. For example, Z is 3-(((methylamino)ethyl)amino)cyclobut-3-enyl-1,2-dione. In some embodiments, Z is cyclobutenyl substituted with one or more of oxygen, sulfur, and monoalkyl or dialkylamino, for example, Z is 2-(diethylamino)-4-thiooxocyclobut-2-en-1-one or 3-(diethylamino)-4-thiooxocyclobut-2-en-1-one.

[0102] In some embodiments, Z is cyclobutenyl substituted with oxygen and one or more of piperidyl, piperazinyl, or morpholinyl. In some embodiments, Z is cyclobutenyl substituted with oxygen and one or more heterocyclyl rings, the heterocyclyl rings being, for example, one or more C-C 12 It is further substituted with an alkyl group. In some embodiments, Z is cyclobutenyl substituted with oxygen and one or more heterocyclyl rings, wherein the heterocyclyl rings (such as piperidyl, piperazinyl, or morpholinyl) are further substituted with methyl. In some embodiments, Z is cyclobutenyl substituted with one or more of oxygen and monoalkyl or dialkylamino, for example, Z is 3-(diethylamino)cyclobut-3-ene-1,2-dione. In some embodiments, Z is cyclobutenyl substituted with sulfur and one or more monoalkyl or dialkylamino, for example, Z is 3-(diethylamino)cyclobut-3-ene-1,2-dithione.

[0103] In some embodiments, Z is cyclobutenyl substituted with one or more of oxygen, sulfur, and monoalkyl or dialkylamino, for example, Z is 3-(ethylamino)-4-thioxocyclobut-2-en-1-one or 2-(ethylamino)-4-thiooxocyclobut-2-en-1-one. In some embodiments, Z is cyclobutenyl substituted with oxygen and one or more monoalkyl or dialkylamino, for example, Z is 3-(ethylamino)cyclobut-3-ene-1,2-dione. In some embodiments, Z is cyclobutenyl substituted with oxygen and one or more monoalkyl or dialkylamino, which are further substituted, for example, with one or more alkoxy groups, e.g., Z is 3-(bis(2-methoxyethyl)amino)cyclobut-3-ene-1,2-dione. In some embodiments, Z is cyclobutenyl substituted with sulfur and one or more monoalkyl or dialkylamino, for example, Z is 3-(ethylamino)cyclobut-3-ene-1,2-dithione.

[0104] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein Z is a 3- to 20-membered heterocyclyl ring. In some embodiments, Z is a 3- to 10-membered heterocyclyl ring, such as a 3-membered heterocyclyl ring, a 4-membered heterocyclyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 7-membered heterocyclyl ring, an 8-membered heterocyclyl ring, a 9-membered heterocyclyl ring, or a 10-membered heterocyclyl ring. In some embodiments, Z is a 3- to 10-membered heterocyclyl ring containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Z is a heteroaryl containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Z is an 8- to 10-membered bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0105] In some embodiments, the present disclosure provides a method for isolating Z from a 5- to 10-membered monocyclic or polycyclic heterocyclyl ring optionally substituted with one or more substituents, wherein the substituents are hydroxyl, oxygen, amino (—NH), mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 may be independently selected from, but are not limited to, alkoxy, halogen, sulfur (=S), a C3-C8 heterocyclyl ring, or aryl, including the above-mentioned amino, mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the alkoxy, C3-C8 heterocyclyl ring, or aryl may be further substituted.

[0106] In some embodiments, the present disclosure provides a compound in which Z is C optionally substituted with one or more substituents. 6-10 aryl (e.g., phenyl) or C 3-6 Cycloalkyl, where the substituents are hydroxyl, oxygen, amino (—NH), mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 may be independently selected from, but are not limited to, alkoxy, halogen, sulfur (=S), a C3-C8 heterocyclyl ring, or aryl, including the above-mentioned amino, mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 The alkoxy, C3-C8 heterocyclyl ring, or aryl may be further substituted, and the amino lipid compound is represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0107] In some embodiments, the present disclosure provides compounds wherein Z is a 5-10 membered heteroaryl optionally substituted with one or more substituents, for example, Z is triazolyl, imidazolyl, pyrimidinyl, purinyl, 2-amino-1,9-dihydro-6H-purin-6-on-9-yl (or guanin-9-yl), adenin-9-yl, cytosin-1-yl, or uracil-1-yl, each of which is hydroxyl, oxygen, amino (—NH), mono- or dialkylamino, C1-C 12 Alkyl, C2-C12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 may be independently selected from, but are not limited to, alkoxy, halogen, sulfur (=S), a C3-C8 heterocyclyl ring, or aryl, including the above-mentioned amino, mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 The alkoxy, C3-C8 heterocyclyl ring, or aryl may be further substituted, and the amino lipid compound is represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0108] In some embodiments, the present disclosure provides a heterocycloalkyl group wherein Z is a 5-14 membered heterocycloalkyl optionally substituted with one or more substituents, wherein the substituents are hydroxyl, oxygen, amino (—NH), mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 may be independently selected from, but are not limited to, alkoxy, halogen, sulfur (=S), a C3-C8 heterocyclyl ring, or aryl, including the above-mentioned amino, mono- or di-alkylamino, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkynyl, C1-C 12 The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the alkoxy, C3-C8 heterocyclyl ring, or aryl may be further substituted.

[0109] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (IA) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein Z is 4-methylpiperazinyl, 4-(4-methoxyphenylmethyl)piperazinyl, isoindolin-2-yl-1,3-dione, pyrrolidin-1-yl-2,5-dione, or imidazolidin-3-yl-2,4-dione.

[0110] In some embodiments, the present disclosure provides that Z is [ka] wherein: Y1 and Y2 are each independently O or S; Each R9 is independently H, halogen, -R b , -N(R b )2, -CN, -N3, -C(=O)OR b , -OC(=O)R b , -OR b , -SR b , -S(-O)R b , -S(=O)OR b , -S(=O)2OR b , -N(R b )2, -N(R b )S(=O)2R b , -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R a OR b )2; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 Provided is an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0111] In some embodiments, the present disclosure provides that Z is [ka] And, [ka] [ka] The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, selected from:

[0112] In some embodiments, the present disclosure provides that Z is [ka] And, [ka] The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, selected from:

[0113] In some embodiments, the present disclosure provides that R [ka] [ka] wherein a is 0, 1, 2, 3, 4, or 5; 10 and R are independently H or C1-C3 hydrocarbyl. 10 is independently C-C hydrocarbyl. In some embodiments, each R 10 is independently C1, C2, or C3 alkyl, or C2 or C3 alkenyl, or C2 or C3 alkynyl.

[0114] In some embodiments, the present disclosure provides R 13 is H, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, the present disclosure provides R 13 is a C1, C2, C3, C4, C5, or C6 hydrocarbyl, or a C1, C2, C3, C4, C5, or C6 heterohydrocarbyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0115] In some embodiments, the present disclosure provides R 13 is C1, C2, C3, C4, C5, or C6 alkyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, R 13 is a C1 or C2 alkyl. In some embodiments, R 13 is a C3 or C4 alkyl. In some embodiments, R 13 is a C5 or C6 alkyl. In some embodiments, the present disclosure provides a method for treating A1 comprising administering to a patient a therapeutically effective amount of a compound selected from the group consisting of: A1 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS( =O)2O, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] The present invention provides an amino lipid compound represented by the above formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0116] In some embodiments, one or more of L, L, L, L, L, and L are substituted with one or more substituents (e.g., L is substituted with one substituent, or L is substituted with multiple substituents; e.g., L and L are substituted with one or more substituents, and when L and L are substituted with one or more substituents, this includes when L is substituted with one substituent or when L is substituted with one substituent; when L and L are substituted with multiple substituents, the multiple substitution occurs on only L, or only L, or on both L and L), and examples of such substituents include -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] These include, but are not limited to: L1, L2, L3, L4, L5, or L6 is -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -Ra OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1, L2, L3, L4, L5, or L6 to form a 3-, 4-, 5-, or 6-membered ring.

[0117] In some embodiments, A2 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] is.

[0118] In some embodiments, Z is a carbocyclyl ring, a heterocyclyl ring, -CN, -OR8, -OL 16 N(R8)2, -C(=O)R8, -C(=O)SR8, -OC(=O)R8, -OC(=O)OR8, -OL 16 OR8, -N(R8)2, -C(=O)N(R8)2, -C(=S)N(R8)2, -S(=O)2R8, -S(=O)2N(R8)2 , -OC(=O)N(R8)2, -C(NR8)N(R8)2, -C(NR8)R8, -C(=O)N(R8)OR8, -CH(R8)N (R8)C(=O)OR8, -C(R8)3, -N(R8)C(=O)R8, -N(R8)C(=O)OR8, -N(R8)S(=O)2 R8, -N(R8)C(=O)N(R8)2, -N(R8)C(=S)N(R8)2, -N(R8)C(NR8)N(R8)2, -N(R 8)C(CHR8)N(R8)2, -N(OR8)C(=O)R8, -N(OR8)S(=O)2R8, -N(OR8)C(=O)OR8, -N(OR8)C(=O)N(R8)2, -N(OR8)C(=S)N(R8)2, -N(OR8)C(NR8)N(R8)2, -N( OR8)C(CHR8)N(R8)2, -OP(=O)(OR8)2, -P(=O)(OR8)2, -C(=N-CN)N(R8)2, -C(=NO-CH3)N(R8)2, -C(=N-SO2-NH2)N(R8)2, or -C(=CH-NO2)N(R8)2.

[0119] In some embodiments, Z is [ka] is.

[0120] In some embodiments, Z is [ka] is selected from.

[0121] In some embodiments, L 15 is a bond. In some embodiments, A1 is -N(R4)-. In some embodiments, A1 is -NH-. In some embodiments, at least two, e.g., 2, 3, 4, 5, or 6 of A1, A2, A3, A4, A5, and A6 are each independently —N(R4)—, —C(═O)O—, —OC(═O)—, —OC(═O)O—, —O—, —C(═O)—, —S—, —C(═O)S—, —SC(═O)—, —C(═O)N(R4)—, —N(R4)C(═O)—, —OC(═O)S—, —SC(═O)O—, —SC(═O)S—, —OC(═O)N(R4)—, —N(R4)C(═O)O—, —N(R4)C(═O)N(R4)—, —SC(═O)N(R4)—, —N(R4)C(═O)S—, —N(C(═O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] is.

[0122] In some embodiments, the present disclosure provides L1, L2, L7, L8, L 11 , L 12, R1, R2, R4, R7, or R9 are each independently substituted with one or more substituents, including, but not limited to, hydroxyl, halogen, alkyl, alkenyl, alkynyl, -CN, oxygen, sulfur, nitrogen, ester group, aryl, cycloalkyl, cycloalkenyl, amido, alkoxy, or alkylthio, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0123] In some embodiments, L1, L2, L7, L8, L 11 , L 12 , R1, R2, R4, R7, or R9 are each independently -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] substituted with one or more substituents, including but not limited to: L1, L2, L7, L8, L 11 , L 12, R1, R2, R4, R7, or R9 are each independently -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b are L1, L2, L7, L8, L 11 , L 12 , R1, R2, R4, R7, or R9 may be linked to a C atom of R1, R2, R4, R7, or R9 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 It is heteroalkynyl.

[0124] In some embodiments, in the amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, none of L1, L2, L3, L4, L5, A1, A2, A3, A4, A5, and A6 is a bond. In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, none of L1, L2, L3, L4, A1, A2, A3, A4, and A5 is a bond, and L6 and A6 are bonds. In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, none of L1, L2, L3, A1, A2, A3, and A4 is a bond, and L5, L6, A5, and A6 are bonds.

[0125] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (I-1): [ka] In the formula, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA).

[0126] In some embodiments, in an amino lipid compound represented by formula (I-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 and R3 is defined as in formula (IA), and R1 and / or R2 is -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 are each independently selected from the group consisting of -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl.

[0127] In some embodiments, in an amino lipid compound represented by formula (I-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA), and none of A1, A2, A3, A4, A5, A6, L1, L2, L3, L4, and L5 is a bond.

[0128] In some embodiments, in an amino lipid compound represented by formula (I-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A7, A8, A9, A 10 , R1, R2, and R3 are as defined in formula (IA), and at least 3, for example 3, 4, 5, or 6 A1, A2, A3, A4, A5, and A6 each independently represent -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] In some embodiments, none of L1, L2, L3, L4, or L5 is a bond.

[0129] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (I-2): [ka] In the formula, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and; At least two, e.g., 2, 3, 4, 5, or 6, A1, A2, A3, A4, A5, and A6 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] In some embodiments, R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 are each independently selected from the group consisting of -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0130] In some embodiments, in an amino lipid compound represented by formula (I-2), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12, A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and; One or more of L1, L2, L3, L4, L5, and L6 are -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] substituted with one or more substituents, including but not limited to: 1 or more of L1, L2, L3, L4, L5, and L6 are -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b, -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1, L2, L3, L4, L5, or L6 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 are each independently selected from the group consisting of -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0131] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (I-3): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L12 , R1, R2, and R3 are as defined in formula (IA), and at least one of A1, A2, A3, A4, A5, and A6 is -N(R4)-, and R4 is as defined in formula (IA).

[0132] In some embodiments, in the amino lipid compound represented by formula (I-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14, A15, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, 10 , L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 and R3 are defined as in formula (IA), at least one of A1, A2, A3, A4, A5, and A6 is -N(R4)-, R4 is defined as in formula (IA), and R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 are further each independently -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl.

[0133] In some embodiments, in an amino lipid compound represented by formula (I-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , R1, R2, and R3 are as defined in formula (IA), wherein at least one of A1, A2, A3, A4, A5, and A6 is -N(R4)-, R4 is as defined in formula (IA), and none of A1, A2, A3, A4, A5, A6, L1, L2, L3, L4, and L5 is a bond.

[0134] In some embodiments, in an amino lipid compound represented by formula (I-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA), and at least three, for example, 3, 4, 5, or 6 of A1, A2, A3, A4, A5, and A6 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O -, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] wherein at least one of the "at least three" is -N(R)-, where R is as defined in formula (IA). In some embodiments, none of L, L, L, L, or L is a bond.

[0135] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (I-4): [ka] In the formula, L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and At least two, for example, 2, 3, 4, 5, or 6 of A1, A2, A3, A4, A5, and A6 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] wherein at least one of the "at least two" is -N(R4)-, where R4 is as defined in formula (IA). In some embodiments, R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be selected from the group consisting of -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0136] In some embodiments, the amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (I-4), wherein L1, L2, L3, L4, L5, L6, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A4, A5, A6, A7, A8, A9, A 10 , R1, R2, and L 15 are defined as in formula (IA), and at least one of A1, A2, A3, A4, A5, and A6 is -N(R4)-, and R4 is defined as in formula (IA), Z is [ka] and One or more of L1, L2, L3, L4, L5, and L6 are -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b, -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] substituted with one or more substituents, including but not limited to: One or more of L1, L2, L3, L4, L5, and L6 is -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1, L2, L3, L4, L5, or L6 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0137] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (IV): [ka] In the formula, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA).

[0138] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (IV-1): [ka] In the formula, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA).

[0139] In some embodiments, in an amino lipid compound represented by formula (IV-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 and R3 is defined as in formula (IA), and R1 and / or R2 are -C(R6)(OL 14A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl.

[0140] In some embodiments, in an amino lipid compound represented by formula (IV-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA), and none of A1, A2, A3, L1, and L2 is a bond.

[0141] In some embodiments, in an amino lipid compound represented by formula (IV-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A7, A8, A9, A 10, R1, R2, and R3 are defined as in formula (IA), and A1, A2, and A3 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] In some embodiments, neither L1 nor L2 is a bond.

[0142] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (IV-2): [ka] In the formula, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and At least two of A1, A2, and A3 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] In some embodiments, R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 are each independently -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0143] In some embodiments, in an amino lipid compound represented by formula (IV-2), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and; At least one of L1, L2, and L3 is -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] substituted with one or more substituents, including but not limited to: One or more of L1, L2, and L3 is -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1, L2, or L3 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0144] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (IV-3): [ka] In the formula, A1, A2, A3, A7, A8, A9, A 10 , L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , R1, R2, and R3 are as defined in formula (IA), and at least one of A1, A2, and A3 is -N(R4)-, and R4 is as defined in formula (IA).

[0145] In some embodiments, in the amino lipid compound represented by formula (IV-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, A1, A2, A3, A7, A8, A9, A 10 , L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 and R3 are as defined in formula (IA), at least one of A1, A2, and A3 is -N(R4)-, R4 is as defined in formula (IA), and R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl.

[0146] In some embodiments, in an amino lipid compound represented by formula (IV-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and R3 are as defined in formula (IA), wherein at least one of A1, A2, A3, and A4 is -N(R4)-, R4 is as defined in formula (IA), and none of A1, A2, A3, L1, and L2 is a bond. In some embodiments, in an amino lipid compound represented by formula (IV-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA), and A1, A2, and A3 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] and at least one of A1, A2, and A3 is -N(R4)-, where R4 is as defined in formula (IA). In some embodiments, neither L1 nor L2 is a bond.

[0147] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (IV-4): [ka] In the formula, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and; At least two, for example, 2, 3, or 4 of A1, A2, and A3 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] wherein at least one of the "at least two" is -N(R4)-, where R4 is as defined in formula (IA). In some embodiments, R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0148] In some embodiments, the amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (IV-4), wherein L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and L 15 are as defined in formula (IA), and at least one of A1, A2, and A3 is -N(R4)-, and R4 is as defined in formula (IA), Z is [ka] and At least one of L1, L2, and L3 is -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -Ra SR b ,or [ka] substituted with one or more substituents, including but not limited to: One or more of L1, L2, and L3 is -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1, L2, or L3 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0149] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V): [ka] In the formula, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA).

[0150] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V-1): [ka] In the formula, L1, L2, L3, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A3, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA).

[0151] In some embodiments, in an amino lipid compound represented by formula (V-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 and R3 is defined as in formula (IA), and R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl.

[0152] In some embodiments, in an amino lipid compound represented by formula (V-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA), and none of A1, A2, A3, and L1 is a bond.

[0153] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V-2): [ka] In the formula, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and A1 and A2 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] In some embodiments, R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0154] In some embodiments, the amino lipid compound represented by formula (V-2), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and; L1 and / or L2 are -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] substituted with one or more substituents, including but not limited to: One or more of L1 and / or L2 is -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1 or L2 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0155] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V-3): [ka] In the formula, A1, A2, A7, A8, A9, A 10 , L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , R1, R2, and R3 are as defined in formula (IA), and at least one of A1 and A2 is -N(R4)-, and R4 is as defined in formula (IA). In some embodiments, in the amino lipid compound represented by formula (IV-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, A1, A2, A7, A8, A9, A 10 , L1, L2, L7, L8, L9, L 10 , L 11 , L 12 and R3 is as defined in formula (IA), at least one of A1 and A2 is -N(R4)-, R4 is as defined in formula (IA), and R1 and / or R2 is -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14A 12 R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl.

[0156] In some embodiments, in an amino lipid compound represented by formula (V-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 , R1, R2, and R3 are as defined in formula (IA), wherein at least one of A1 and A is -N(R4)-, R4 is as defined in formula (IA), and none of A1, A2, and L1 is a bond. In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V-4): [ka] In the formula, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and A1 and / or A2 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] and at least one of A1 and A2 is -N(R4)-, where R4 is as defined in formula (IA). In some embodiments, R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0157] In some embodiments, the amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (V-4): In the formula, L1, L2, L7, L8, L9, L 10 , L 11 , L 12 , A1, A2, A7, A8, A9, A 10 , R1, R2, and L 15 are as defined in formula (IA), and at least one of A1 and A2 is -N(R4)-, and R4 is as defined in formula (IA), Z is [ka] and; L1 and / or L2 are -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -Ra SR b ,or [ka] substituted with one or more substituents, including but not limited to: L1 and / or L2 are -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1 or L2 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), wherein R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0158] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V-5): [ka] In the formula, R1 and R2 are each independently C1-C 24 Hydrocarbyl, -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7)R7, L1, L7, L8, L9, L 10 , L 11 , L 12 , A7, A8, A9, A 10 , R4, R9, Y1, Y2, R6, L 14 , A 12 and R7 are as defined in formula (IA).

[0159] In some embodiments, the amino lipid compound represented by formula (V-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (V-5-1): [ka]

[0160] In some embodiments, in the amino lipid compound represented by formula (V-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V-5-2): [ka] Y1 and Y2 are each independently O or S; R9 is H, halogen, -R b , -N(R b )2, -CN, -N3, -C(=O)OR b , -OC(=O)R b , -OR b , -SR b , -S(-O)R b , -S(=O)OR b , -S(=O)2OR b , -N(R b )S(=O)2R b , -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R a OR b )2; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 is heteroalkynyl; L1 is a C1-C6 hydrocarbylene, a C3-C8 carbocyclyl ring, or a C1-C6 heterohydrocarbylene; L7 and L8 are each independently C1-C 10 is hydrocarbylene; L 11 and L 12 are each independently a C1-C5 hydrocarbylene or a bond; A7 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] and; A8 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13OR4)-, -OC(=O)C(=O)O-, [ka] or is a bond; R1 and R2 are each independently C1-C 24 alkyl, -C(R6)(OR7)2, -C(R6)(SR7)2, or -C(R6)(SR7)(OR7); Each R7 is independently 12 is a hydrocarbyl; L9, L 10 , A9, and A 10 is a bond; R4, L 13 and R6 are defined as in formula (V-5).

[0161] The amino lipid compounds of formula (V-5), (V-5-1), or (V-5-2), or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprise one or more of the following characteristics, as applicable: In some embodiments, Y 1 is O. In some embodiments, Y2 is O. In some embodiments, Y 1 and Y 2 are O. In some embodiments, R9 is —N(R b )2, -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R a OR b )2. In some embodiments, R9 is —N(R b )2 or -NHR a N(R b )2. In some embodiments, R9 is —N(R b )2. In some embodiments, R9 is —N(H)CH3. In some embodiments, Y and Y are each independently O or S, and R is —N(R b )2 or -NHR a N(R b )2. In some embodiments, Y and Y are O and R is —N(R b )2. In some embodiments, Y1 and Y2 are O and R9 is -N(H)CH3. In some embodiments, each R a are independently C1-C 12 It is alkylene. In some embodiments, each R a is independently C1-C5 alkylene. In some embodiments, each R b are independently H, C1-C 12 Alkyl, or C2-C 12 It is alkenyl. In some embodiments, each R b is independently H, C1-C6 alkyl, or C2-C3 alkenyl. In some embodiments, each R b are independently H, or C1-C3 alkyl. In some embodiments, each R b is independently H, or C1-C2 alkyl, for example C1 alkyl.

[0162] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] is.

[0163] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, or -OC(=O)C(=O)O-. In some embodiments, A7 and A8 are each independently -C(=O)O- or -OC(=O)-. In some embodiments, A7, A8, A9, and A 10 are each independently -C(=O)O-, -OC(=O)-, or a bond. In some embodiments, A7 is -C(=O)O-. In some embodiments, A7 is -OC(=O)-. In some embodiments, A8 is -C(=O)O-. In some embodiments, A8 is -OC(=O)-. In some embodiments, A7 and A8 are -C(=O)O-. In some embodiments, A7 and A8 are -OC(=O)-. In some embodiments, A8 is a bond. In some embodiments, A9 is -C(=O)O-. In some embodiments, A9 is -OC(=O)-. In some embodiments, A 10 is -C(=O)O-. In some embodiments, A 10 is -OC(=O)-. In some embodiments, A9 is a bond. In some embodiments, A 10 is a bond. In some embodiments, A and A 10 is -C(=O)O-. In some embodiments, A and A 10 is a bond.

[0164] In some embodiments, R and R are each independently C-C 24alkyl, -C(R6)(OR7)2, -C(R6)(C(=O)OR7)2, -C(R6)(OC(=O)R7)2, -C(R6)(C(=O)OR7)R7, or -C(R6)(OC(=O)R7)R7. In some embodiments, R and R are each independently C-C 24 It is alkyl. In some embodiments, R is a straight chain C-C 18 It is alkyl. In some embodiments, R is a straight chain C-C 15 It is alkyl. In some embodiments, R1 is a straight chain C4-C 12 It is alkyl. In some embodiments, R1 is a straight chain C5-C alkyl, such as a C5 alkyl, a C6 alkyl, or a C9 alkyl. 10 It is alkyl. In some embodiments, R1 is a straight chain C7-C alkyl, such as a C7 alkyl, a C8 alkyl, or a C9 alkyl. 10 It is alkyl.

[0165] In some embodiments, R is a branched C9-C 18 Alkyl, branched C9-C 17 Alkyl, branched C 10 -C 18 Alkyl, branched C 11 -C 17 Alkyl, branched C 12 -C 17 Alkyl, branched C 12 Alkyl, branched C 14 Alkyl, branched C 16 Alkyl, or branched C 17 Branched C9-C alkyl 20 It is alkyl. In some embodiments, R2 is a straight chain C1-C 18 It is alkyl. In some embodiments, R2 is a straight chain C1-C 15 It is alkyl. In some embodiments, R2 is a straight chain C4-C 12 It is alkyl. In some embodiments, R2 is a straight chain C5-C alkyl, such as a C5 alkyl, a C6 alkyl, or a C9 alkyl. 10 It is alkyl. In some embodiments, R2 is a straight chain C7-C alkyl, such as a C7 alkyl, a C8 alkyl, or a C9 alkyl. 10 It is alkyl.

[0166] In some embodiments, R2 is a branched C9-C 18 Alkyl, branched C9-C 17 Alkyl, branched C 10 -C 18 Alkyl, branched C 11 -C 17 Alkyl, branched C 12 -C 17 Alkyl, branched C 12 Alkyl, branched C 14 Alkyl, branched C 16 Alkyl, or branched C 17 Branched C9-C alkyl 20 It is alkyl. In some embodiments, R1 is a straight chain C5-C 10 alkyl, and R2 is a branched C9-C 20 It is alkyl. In some embodiments, R1 is a straight chain C4-C 12 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, R1 is a straight chain C7-C 10 alkyl, and R2 is a branched C9-C 17 It is alkyl. In some embodiments, R1 and R2 are branched C9-C 20 It is alkyl. In some embodiments, R is a branched C9-C 18 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, R is a branched C9-C 17 alkyl, and R2 is a branched C9-C 17 It is alkyl.

[0167] In some embodiments, L 11 is a bond, and the branching of R1 occurs at the α, β, or γ position of A9, for example, the branching of R1 occurs at the α position of A9: [ka] Branching of R1 occurs at the β position of A9. [ka]

[0168] In some embodiments, L9, A9, and L 11 is a bond and the branching of R1 occurs at the α, β, or γ position of A7. In some embodiments, the branching of R1 occurs at the α or β position of A7.

[0169] In some embodiments, L 12 is a bond, and the branch of R2 is A 10 For example, the branching of R2 occurs at the α, β, or γ position of A 10 occurs at the alpha position of: [ka] The branch of R2 is A 10 It occurs at the β position of [ka] In some embodiments, L 10 , A 10 , and L 12 is a bond and the branching of R2 occurs at the α, β, or γ position of A8. In some embodiments, the branching of R2 occurs at the α or β position of A8.

[0170] In some embodiments, R1 or R2 has the following structure: [ka] It is one of the following.

[0171] In some embodiments, R1 is C(H)(OR7)2. In some embodiments, R1 is -C(H)(C(=O)OR7)2. In some embodiments, R1 is -C(H)(OC(=O)R7)2. In some embodiments, R2 is -C(H)(OR7)2. In some embodiments, R2 is -C(H)(C(=O)OR7)2. In some embodiments, R2 is -C(H)(OC(=O)R7)2. In some embodiments, R1 is -C(H)(OR7)2 and R2 is a straight chain C5-C 10 It is alkyl. In some embodiments, R1 and R2 are -C(H)(OR7)2. In some embodiments, R1 and R2 are -C(H)(C(=O)OR7)2. In some embodiments, each R is independently C-C 12 It is alkyl. In some embodiments, each R is independently a C3-C alkyl, such as a C5-C7 alkyl or a C6 alkyl. 10 It is alkyl. In some embodiments, each R7 is independently a substituted C3-C 10 It is alkyl. In some embodiments, L1 is C1-C6 alkylene. In some embodiments, L1 is C2-C5 alkylene. In some embodiments, L1 is C2-C4 alkylene. In some embodiments, L1 is C3-C4 alkylene. In some embodiments, L1 is C3 alkylene.

[0172] In some embodiments, L1 is a substituted C2-C4 alkylene, for example, L1 is a C3 alkylene substituted with hydroxy, for example, [ka] is. In some embodiments, each R4 is independently H or C1-C6 alkyl. In some embodiments, R4 is C1-C6 alkyl. In some embodiments, R4 is C2-C5 alkyl, such as C2 alkylene, C3 alkylene, or C5 alkylene. In some embodiments, each R4 is independently H or C1-C2 alkyl. In some embodiments, R4 is C1-C2 alkyl. In some embodiments, R4 is methyl.

[0173] In some embodiments, R4 is a branched C3-C6 alkyl, e.g. [ka] is. In some embodiments, R4 is a substituted C1-C6 alkyl, for example, -OH, -OC(=O)R b , or -C(=O)OR b wherein each R b are independently C1-C 12 Alkyl, C2-C 12 Alkenylene, or C2-C 12 It is alkynylene.

[0174] In some embodiments, R4 is a C1-C6 alkyl substituted with -OH, e.g., R4 is a C2 alkyl substituted with -OH, e.g., [ka] is.

[0175] In some embodiments, R4 is -OC(=O)R b or -C(=O)OR b wherein each R bare independently C1-C7 alkyl, e.g. [ka] is.

[0176] In some embodiments, L7 and L8 are each independently C1-C 14 alkylene, or a bond. In some embodiments, L7 is C1-C 10 It is alkylene. In some embodiments, L7 is a C4-C8 alkylene, such as a C5 alkylene, a C6 alkylene, or a C7 alkylene. In some embodiments, L8 is C1-C 10 It is alkylene. In some embodiments, L8 is a C4-C8 alkylene, such as a C5 alkylene, a C6 alkylene, or a C7 alkylene. In some embodiments, L7 is a bond. In some embodiments, L8 is a bond. In some embodiments, L7 and L8 are each independently C1-C 10 It is alkylene. In some embodiments, L7 and L8 are each independently a C3-C9 alkylene. In some embodiments, L7 and L8 are each independently a C4-C8 alkylene, such as a C5 alkylene, a C6 alkylene, or a C7 alkylene. In some embodiments, L7 and L8 are a bond. In some embodiments, L7 and L8 are each independently a C1-C3 alkylene or a bond.

[0177] In some embodiments, L7 and L8 are each independently a branched C2-C3 alkylene, e.g., a branched C2 alkylene [ka] is. In some embodiments, L7 is C1-C3 alkylene and L8 is branched C2-C3 alkylene. In some embodiments, L7 is a bond and L8 is a branched C2-C3 alkylene. In some embodiments, L and L 10 are each independently a C4-C7 alkylene.

[0178] In some embodiments, L and L 10 are each independently a branched C4-C7 alkylene, for example, [ka] is.

[0179] In some embodiments, L9 is a bond. In some embodiments, L 10 is a bond. In some embodiments, L and L 10 is a bond. In some embodiments, L 11 is C1-C5 alkylene. In some embodiments, L 11 is C2-C4 alkylene, for example, C3 alkylene. In some embodiments, L 11 is a bond. In some embodiments, L 11 is a C2-C4 alkylene or a bond. In some embodiments, L 12 is C1-C5 alkylene. In some embodiments, L 12 is C2-C4 alkylene, for example, C3 alkylene. In some embodiments, L 12 is a bond. In some embodiments, L 12 is a C2-C4 alkylene or a bond. In some embodiments, L 11is a bond and L 12 is C2-C4 alkylene, for example, C3 alkylene.

[0180] In some embodiments, L9, L 10 , L 11 , and L 12 is a bond, A7 is -C(=O)O- or -OC(=O)-, A8 is -C(=O)O- or -OC(=O)-, A9 and A 10 is a bond, and R1 and R2 are each independently C1-C 24 In some embodiments, R and R are each independently a branched C alkyl. 10 -C 18 Alkyl, branched C 11 -C 17 Alkyl, branched C 12 -C 17 Alkyl, branched C 12 Alkyl, branched C 14 Alkyl, branched C 16 Alkyl, or branched C 17 Branches such as C9-C 20 It is alkyl.

[0181] In some embodiments, A7, A8, A9, and A 10 are each independently -C(=O)O- or -OC(=O)-, and L and L 10 are each independently a C4-C7 alkylene; L 11 and L 12 is a bond, and R1 and R2 are C9-C 20 In some embodiments, L and L are alkyl. 10 is a branched C4-C7 alkylene. In some embodiments, L9 and L 10 is a branched C6 alkyl, e.g. [ka] In some embodiments, R1 and R2 are branched C9-C 20 In some embodiments, R and R are each a branched C alkyl.12 Alkyl, for example, [ka] is.

[0182] In some embodiments, L9, L 10 , A9, and A 10 is a bond, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, and R1 and R2 are -C(H)(OR7)2. In some embodiments, each R7 is independently C1-C 12 In some embodiments, each R is independently a C3-C alkyl, such as a C5-C7 alkyl or a C6 alkyl. 10 It is alkyl. In some embodiments, L9, L 10 , A9, and A 10 is a bond, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, R1 is -C(H)(OR7)2, and R2 is C6-C 12 It is alkyl. In some embodiments, L9, L 10 , A9, and A 10 is a bond, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, and R1 and R2 are -C(R6)(C(=O)OR7)2 or -C(R6)(OC(=O)R7)2. In some embodiments, R1 and R2 are -C(H)(C(=O)OR7)2. In some embodiments, L7, L8, L9, L 10 , A9, and A 10 is a bond, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, and R1 and R2 are -C(H)(OR7)2.

[0183] In some embodiments, the amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound has a structure represented by formula (V-6): [ka] In the formula, R1 and R2 each independently represent -C(R6)(SL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7)R7, L1, L7, L8, L 11 , L 12 , L 15 , A7, A8, R4, R6, L 14 , A 12 and R7 are as defined in formula (IA).

[0184] In some embodiments, the amino lipid compound represented by formula (V-6), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (V-6-1): [ka] During the ceremony: L1 is C1-C6 hydrocarbylene or C1-C6 heterohydrocarbylene; L 15 is C1-C2 hydrocarbylene; L7 and L8 are each independently C1-C 10 is hydrocarbylene; L 11 and L 12 are each independently C1-C5 hydrocarbylene; A7 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] and; A8 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] or is a bond; R1 and R2 are each independently -C(R6)(C(=O)OR7)2, -C(R6)(OC(=O)R7)2, -C(R6)(C(=O)OR7)R7, or -C(R6)(OC(=O)R7)R7; Each R7 is independently 12 is a hydrocarbyl; R4, L 13 and R6 are defined as in formula (V-6).

[0185] The amino lipid compounds of formula (V-6) or (V-6-1), or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprise one or more of the following characteristics, where applicable:

[0186] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] is. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, or -OC(=O)C(=O)O-. In some embodiments, A7 and A8 are each independently -C(=O)O- or -OC(=O)-. In some embodiments, A7 is -C(=O)O. In some embodiments, A7 is -OC(=O)-. In some embodiments, A8 is -C(=O)O-. In some embodiments, A8 is -OC(=O)-. In some embodiments, A7 and A8 are each -C(=O)O-. In some embodiments, A8 is a bond.

[0187] In some embodiments, R1 and R2 are each independently -C(H)(C(=O)OR7)2, -C(H)(OC(=O)R7)2-, C(H)(C(=O)OR7)R7, or -C(H)(OC(=O)R7)R7. In some embodiments, R1 is -C(H)(C(=O)OR7)2. In some embodiments, R1 is -C(H)(OC(=O)R7)2. In some embodiments, R1 is -C(H)(C(=O)OR7)R7. In some embodiments, R1 is -C(H)(OC(=O)R7)R7. In some embodiments, R2 is -C(H)(C(=O)OR7)2. In some embodiments, R2 is -C(H)(OC(=O)R7)2. In some embodiments, R2 is -C(H)(C(=O)OR7)R7. In some embodiments, R2 is -C(H)(OC(=O)R7)R7. In some embodiments, R1 and R2 are each -C(H)(OC(=O)R7)2. In some embodiments, R1 and R2 are each -C(H)(C(=O)OR7)R7. In some embodiments, L 15 is C1-C2 alkylene. In some embodiments, L 15 is a C1 alkylene. In some embodiments, R4 is C1-C3 alkyl. In some embodiments, R4 is C1 alkyl. In some embodiments, L1 is C2-C4 alkylene. In some embodiments, L1 is C3 alkylene.

[0188] In some embodiments, L7 and L8 are each independently C1-C 10 It is alkylene. In some embodiments, L7 and L8 are each independently a C3-C9 alkylene. In some embodiments, L7 and L8 are each independently C3-C8 alkylene. In some embodiments, L7 and L8 are each independently a C4-C7 alkylene, such as a C5-C7 alkylene, a C5 alkylene, or a C6 alkylene. In some embodiments, L 11 and L 12 are each independently a C2-C4 alkylene, such as a C2 alkylene or a C3 alkylene. In some embodiments, each R7 is independently C3-C9 alkyl. In some embodiments, each R7 is independently C5-C7 alkyl. In some embodiments, each R7 is independently C6 alkyl.

[0189] In some embodiments, A7 and A8 are -C(=O)O-, R1 and R2 are -C(H)(C(=O)OR7)2, and each R7 is independently C3-C9 alkyl. In some embodiments, each R7 is independently C5-C7 alkyl. In some embodiments, R7 is C5 alkyl. In some embodiments, R7 is C6 alkyl. In some embodiments, A7 and A8 are -C(=O)O-, R1 and R2 are -C(H)(OC(=O)R7)R7, and each R7 is independently C3-C9 alkyl. In some embodiments, each R7 is independently C5-C7 alkyl, such as C5 alkyl or C6 alkyl. In some embodiments, each R7 is C5 alkyl or C6 alkyl, e.g., R1 and R2 are -C(H)(OC(=O)C5H 11 )C6H 13 is.

[0190] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (VI): [ka] In the formula, L1, L7, L8, L9, L 10 , L 11 , L 12 , A1, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA).

[0191] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (VI-1): [ka] In the formula, L1, L7, L8, L9, L 10 , L 11 , L 12 , A1, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA).

[0192] In some embodiments, in the amino lipid compound represented by formula (VI-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L7, L8, L9, L 10 , L 11 , L 12 , A1, A7, A8, A9, A 10 and R3 is defined as in formula (IA), and R1 and / or R2 is -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl. In some embodiments, in the amino lipid compound represented by formula (VI-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L7, L8, L9, L 10 , L 11, L 12 , A1, A7, A8, A9, A 10 , R1, R2, and R3 are defined as in formula (IA), and neither A1 nor L1 is a bond.

[0193] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (VI-2): [ka] In the formula, L1, L7, L8, L9, L 10 , L 11 , L 12 , A1, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and; L1 is -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R aSR b ,or [ka] substituted with one or more substituents, including but not limited to: At least one L1 is -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), where R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0194] In some embodiments, A1 is -N(R4)-. In some embodiments, R4 is H.

[0195] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (VI-3): [ka] In the formula, A1, A7, A8, A9, A 10 , L1, L7, L8, L9, L 10 , L 11 , L 12 , R1, R2, and R3 are as defined in formula (IA), A1 is -N(R4)-, and R4 is as defined in formula (IA).

[0196] In some embodiments, in the amino lipid compound represented by formula (VI-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, A1, A7, A8, A9, A 10 , L1, L7, L8, L9, L 10 , L 11 , L 12 and R3 is as defined in formula (IA), A1 is -N(R4)-, R4 is as defined in formula (IA), and R1 and / or R2 are -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), and R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R)R. In some embodiments, each R is independently C, C, C, C, C, C, or C alkyl. In some embodiments, each R is independently C, C, or C alkyl. In some embodiments, in the amino lipid compound represented by formula (VI-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, L1, L7, L8, L9, L 10 , L 11 , L 12 , A1, A7, A8, A9, A 10 , R1, R2, and R3 are as defined in formula (IA), wherein A1 is -N(R4)-, R4 is as defined in formula (IA), and neither A1 nor L1 is a bond.

[0197] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (VI-4): [ka] In the formula, L1, L7, L8, L9, L 10 , L 11 , L 12 , A1, A7, A8, A9, A 10 , R1, R2, and L 15 is defined as in formula (IA), Z is [ka] and; A1 is -N(R4)-, where R4 is as defined in formula (IA), and L1 is -OH, -SH, halogen, O, S, N, -CN, cyclohydrocarbyl, aryl, heterocyclyl, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] substituted with one or more substituents, including but not limited to: L1 is -R b , -R a OR b , -R a SR b、 -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)Rb , -C(=O)OR b , -R a SR b ,or [ka] When substituted with a substituent containing a and / or R b may be linked to a C atom of L1 to form a 3-, 4-, 5-, or 6-membered ring; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12In some embodiments, R and / or R are -C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), where R6, L 14 , A 12 and R7 are as defined in formula (IA). In some embodiments, R1 and R2 can each independently be -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0198] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (VI-5): [ka] In the formula, R1 and R2 are each independently C1-C 24 Hydrocarbyl, -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7)R7, L7, L8, L 11 , L 12 , L 15 , A7, A8, R4, R6, L 14 , A 12 and R7 are as defined in formula (IA).

[0199] In some embodiments, the amino lipid compound represented by formula (VI-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (VI-5-1): [ka] During the ceremony: L 15 is C1-C2 hydrocarbylene; R4 is C1-C6 hydrocarbyl or C1-C6 heterohydrocarbyl; L7 and L8 are each independently C1-C 10 is hydrocarbylene; L 11 and L 12 are each independently C1-C5 hydrocarbylene; A7 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] and; A8 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] or is a bond; R1 and R2 are each independently -C(R6)(OR7)2, -C(R6)(SR7)2, or -C(R6)(SR7)(OR7); Each R7 is independently 12 is a hydrocarbyl; L 13 and R6 is as defined in formula (VI-5).

[0200] The amino lipid compounds of formula (VI-5) or (VI-5-1), or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprise one or more of the following characteristics, where applicable: In some embodiments, A7 and A8 are each C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] is.

[0201] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, or -OC(=O)C(=O)O-. In some embodiments, A7 and A8 are each independently -C(=O)O- or -OC(=O)-. In some embodiments, A7 is -C(=O)O-. In some embodiments, A7 is -OC(=O)-. In some embodiments, A8 is -C(=O)O-. In some embodiments, A8 is -OC(=O)-. In some embodiments, A7 and A8 are -C(=O)O-. In some embodiments, A8 is a bond.

[0202] In some embodiments, R1 and R2 are each independently -C(H)(OR7)2, -C(H)(C(=O)OR7)2, -C(H)(OC(=O)R7)2-, C(H)(C(=O)OR7)R7, or -C(H)(OC(=O)R7)R7. In some embodiments, R1 is C(H)(OR7)2. In some embodiments, R2 is -C(H)(OR7)2. In some embodiments, R1 and R2 are each -C(H)(OR7)2. In some embodiments, L 15 is C1-C2 alkylene. In some embodiments, L 15 is a C1 alkylene. In some embodiments, R4 is C1-C3 alkyl. In some embodiments, R4 is C1 alkyl.

[0203] In some embodiments, L7 and L8 are each independently C1-C 10 It is alkylene. In some embodiments, L7 and L8 are each independently a C3-C9 alkylene. In some embodiments, L7 and L8 are each independently a C4-C8 alkylene. In some embodiments, L7 and L8 are each independently a C4-C7 alkylene. In some embodiments, L7 and L8 are each independently a C5-C7 alkylene, such as a C5 alkylene or a C6 alkylene. In some embodiments, L 11 and L 12 are each independently a C2-C4 alkylene, such as a C2 alkylene or a C3 alkylene. In some embodiments, each R7 is independently C3-C9 alkyl. In some embodiments, each R7 is independently a C5-C7 alkyl, such as a C6 alkyl.

[0204] In some embodiments, A7 and A8 are each -C(=O)O-, L7 and L8 are each independently C4-C8 alkylene, and R1 and R2 are -C(H)(OR7)2. In some embodiments, each R7 is independently C5-C7 alkyl, such as C6 alkyl.

[0205] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (V-7): [ka] During the ceremony: Y1 and Y2 are each independently O or S; Each R9 is independently H, halogen, -R b , -N(R b )2, -CN, -N3, -C(=O)OR b , -OC(=O)R b , -OR b , -SR b , -S(-O)R b , -S(=O)OR b , -S(=O)2OR b , -N(R b )S(=O)2R b , -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R aOR b )2; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylheteroalkyl, C2-C containing one, two, three or more triple bonds 12 Alkynylheteroalkyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 is heteroalkynyl; L1 and L2 are each independently a C1-C6 hydrocarbylene, a C3-C8 carbocyclyl ring, or a C1-C6 heterohydrocarbylene; L7 and L8 are each independently C1-C 10 is hydrocarbylene; L 11 and L 12are each independently a C1-C5 hydrocarbylene or a bond; A2 and A7 are each independently -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)- , -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -SC(=O)N(R4)-, -N(R4)C(=O)S-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -N(L 13 SR4)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(= O)2O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] and; R1 and R2 are each independently C1-C 24 Hydrocarbyl, -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12R7)R7; Each R7 is independently 12 is a hydrocarbyl; A8, R4, R6, L 13 , L 14 , and A 12 is defined as in formula (IA).

[0206] In some embodiments, the amino lipid compound represented by formula (V-7), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (V-7-1) or (V-7-2): [ka] During the ceremony, A7 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] and; A8 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] or is a bond; R1 and R2 are each independently C1-C 24 alkyl, -C(R6)(OR7)2, -C(R6)(SR7)2, or -C(R6)(SR7)(OR7); L1, L2, L7, L8, L 11, L 12 , L 13 , R4, R6, R7, R9, Y1, and Y2 are defined as in formula (V-7).

[0207] In some embodiments, the present disclosure provides compounds wherein A7 and A8 are each independently —C(═O)O— or —OC(═O)—; and L 11 is a bond and L 12 is a bond, and R1 and R2 are each independently a straight chain C4-C 12 Alkyl or branched C9-C 18 The present invention provides an amino lipid compound represented by formula (V-7-1) or (V-7-2), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein V-7-1 is alkyl. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (V-7-1) or (V-7-2), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A7 and A8 are each independently -C(=O)O- or -OC(=O)-, and R1 and R2 are each independently -C(H)(OR7)2.

[0208] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (VI-6): [ka] During the ceremony, Y1 and Y2 are each independently O or S; Each R9 is independently H, halogen, -R b , -N(R b )2, -CN, -N3, -C(=O)OR b , -OC(=O)R b , -OR b , -SR b , -S(-O)R b , -S(=O)OR b , -S(=O)2OR b , -N(R b )S(=O)2Rb , -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R a OR b )2; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 is heteroalkynyl; L1 is a C1-C6 hydrocarbylene, a C3-C8 carbocyclyl ring, or a C1-C6 heterohydrocarbylene; L7 and L8 are each independently C1-C 10 is hydrocarbylene; L 11 and L 12 are each independently a C1-C5 hydrocarbylene or a bond; A7, A8, R4, R1, and R2 are one selected from the following: (1) R1 and R2 are each independently -C(R6)(OR7)2, -C(R6)(SR7)2, or -C(R6)(SR7)(OR7); A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -OC(=O)C(=O)O-, -O-, -SC(=O)O-, -OC(=O)S-, -C(=O)N(R4)-, or -N(R4)C(=O)-; R4, R6, and R7 are as defined in formula (IA); (2) R1 and R2 are each independently C1-C 24 A7 is -OC(=O)S- or -SC(=O)O-; A8 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -SC(=O)O-, -OC(=O)S-, -C(=O)N(R4)-, -N(R4)C(=O)-, or -OC(=O)C(=O)O-; R4 is as defined in formula (IA); and (3) R1 and R2 are each independently C1-C 24 A7 and A8 are -OC(=S)O-; R4 is as defined in formula (IA).

[0209] In some embodiments, in an amino lipid compound represented by formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, the amino lipid compound has a structure represented by formula (IV-5): [ka] During the ceremony: Y1 and Y2 are each independently O or S; Each R9 is independently H, halogen, -R b , -N(R b )2, -CN, -N3, -C(=O)OR b , -OC(=O)R b , -OR b , -SR b , -S(-O)R b , -S(=O)OR b , -S(=O)2OR b , -N(R b )S(=O)2R b , -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R a OR b )2; Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 is heteroalkynyl; L1 and L2 are each independently C1-C6 hydrocarbylene; L3 is a C1-C6 hydrocarbylene or a bond; L7 and L8 are each independently C1-C 10 is a hydrocarbylene or bond; L 11 and L 12 are each independently a C1-C5 hydrocarbylene or a bond; A3 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] and; A7 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L13 OR4)-, -OC(=O)C(=O)O-, [ka] and; A8 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] or is a bond; R1 and R2 are each independently C1-C 24 alkyl, —C(R6)(OR7)2, —C(R6)(SR7)2, or —C(R6)(SR7)(OR7); L9, L 10 , L 13 , A9, A 10 , R4, R6, or R7 are defined as in formula (IA).

[0210] In some embodiments, the amino lipid compound represented by formula (IV-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (IV-5-1): [ka] During the ceremony: R1 and R2 are each independently -C(R6)(OR7)2, and L1, L2, L7, L8, L 11 , L 12 , A3, A7, A8, R4, R6, R7, R9, Y1, and Y2 are defined as in formula (IA-5). The amino lipid compounds of formula (V-7), (V-7-1), (V-7-2), (VI-6), (IV-5), or (IV-5-1), or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprise one or more of the following characteristics, as applicable:

[0211] In some embodiments, Y 1 and Y 2 are each independently O or S. In some embodiments, Y 1 is O. In some embodiments, Y2 is O. In some embodiments, Y 1 and Y 2 are O. In some embodiments, R9 is —N(R b )2, -NHR a N(R b )2, -NHR a OR a N(R b )2, -NHR a OR b , or -N(R a OR b )2. In some embodiments, R9 is —N(R b )2 or -NHR a N(R b )2. In some embodiments, R9 is —N(R b )2. In some embodiments, R9 is —N(H)CH3. In some embodiments, Y and Y are each independently O or S, and R is —N(R b )2 or -NHR a N(R b )2. In some embodiments, Y and Y are O and R is —N(R b )2. In some embodiments, Y1 and Y2 are O and R9 is -N(H)CH3. In some embodiments, each R a are independently C1-C 12 It is alkylene. In some embodiments, each R a is independently C1-C5 alkylene. In some embodiments, each R b are independently H, C1-C 12 Alkyl, or C2-C 12 It is alkenyl. In some embodiments, each R b is independently H, C1-C6 alkyl, or C2-C3 alkenyl. In some embodiments, each R b are independently H, or C1-C3 alkyl. In some embodiments, each R b is independently H, or C1-C2 alkyl, for example C1 alkyl. In some embodiments, each R4 is independently H or C1-C6 alkyl.

[0212] In some embodiments, A2 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] is.

[0213] In some embodiments, A2 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, or -N(R4)C(=O)C(=O)N(R4)-. In some embodiments, A2 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)C(=O)O-, or -N(R4)C(=O)C(=O)O-. In some embodiments, A2 is -C(=O)O-, -OC(=O)O-, -OC(=O)-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A2 is -C(=O)N(R4)- or -N(R4)C(=O)-. In some embodiments, A2 is -C(=O)NH-. In some embodiments, A2 is -NHC(=O)-.

[0214] In some embodiments, A3 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] is.

[0215] In some embodiments, A3 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, or -N(R4)C(=O)C(=O)N(R4)-. In some embodiments, A3 is -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, or -N(R4)C(=O)O-. In some embodiments, A3 is -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(H)-, -N(H)C(=O)-, -OC(=O)N(H)-, or -N(H)C(=O)O-. In some embodiments, A3 is -OC(=O)O-, -N(H)C(=O)-, or -C(=O)N(H)-. In some embodiments, A3 is -OC(=O)O-, -N(H)C(=O)O-, or -OC(=O)N(H)-.

[0216] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -O-, -SC(=O)O-, -OC(=O)S-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] is.

[0217] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, -OC(=O)C(=O)O-, [ka] is.

[0218] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, or -OC(=O)C(=O)O-. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, or -OC(=O)O-. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -O-, -SC(=O)O-, -OC(=O)S-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -O-, -SC(=O)O-, -OC(=O)S-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A7 is -C(=O)N(H)- or -N(H)C(=O)-.

[0219] In some embodiments, A8 is -C(=O)O-, -OC(=O)-, -O-, -SC(=O)O-, -OC(=O)S-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A8 is -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A8 is -SC(=O)O- or -OC(=O)S-. In some embodiments, A7 and A8 are each independently -C(=O)O- or -OC(=O)-. In some embodiments, A7 is -C(=O)O-. In some embodiments, A7 is -OC(=O)-. In some embodiments, A8 is -C(=O)O-. In some embodiments, A8 is -OC(=O)-. In some embodiments, A7 and A8 are -C(=O)O-. In some embodiments, A7 and A8 are -OC(=O)-. In some embodiments, A7 is -C(=O)O- and A8 is -OC(=O)-. In some embodiments, A7 is -OC(=O)- and A8 is -C(=O)O-. In some embodiments, A7 is -O- and A8 is -C(=O)O-. In some embodiments, A7 and A8 are -O-. In some embodiments, A7 is -C(=O)N(H)- and A8 is -C(=O)O-. In some embodiments, A8 is -C(=O)N(H)- or -N(H)C(=O)-. In some embodiments, A7 and A8 are -SC(=O)O-. In some embodiments, A7 and A8 are -OC(=O)S-. In some embodiments, A7 is -C(=O)O- and A8 is -OC(=O)S-.

[0220] In some embodiments, A7 is -C(O)O-, -OC(O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and A8 is -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -SC(=O)O-, or -OC(=O)S-, and A8 is -SC(=O)O- or -OC(=O)S-. In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -OC(=S)O-, -SC(=O)O-, or -OC(=O)S-, and A8 is -SC(=O)O-, -OC(=O)S-, or -OC(=S)O-. In some embodiments, A8 is a bond. In some embodiments, A8 is —C(═O)O—, —OC(═O)—, —O—, —SC(═O)O—, —OC(═O)S—, —C(═O)N(R4)—, —N(R4)C(═O)—, —N(C(═O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, or -OC(=O)C(=O)O-, and A7 is -C(=O)S- or -SC(=O)-. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(H)-, or -N(H)C(=O)-. In some embodiments, A7 and A8 are each independently -C(=O)O- or -OC(=O)-.

[0221] In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A8 is -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-. In some embodiments, A8 is -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and R1 and R2 are each independently -C(R6)(OR7)2. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and R1 and R2 are each independently -C(R6)(OR7)2, -C(R6)(SR7)2, or -C(R6)(SR7)(OR7). In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and R1 and R2 are each independently -C(R6)(OR7)2. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and R1 and R2 are each independently -C(R6)(SR7)2 or -C(R6)(SR7)(OR7). In some embodiments, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, and R1 and R2 are each independently -C(R6)(SR7)2 or -C(R6)(SR7)(OR7).

[0222] In some embodiments, A and A 10 are each independently -OC(=O)-, -C(=O)O-, or a bond. In some embodiments, A9 is -OC(=O)-. In some embodiments, A9 is -C(=O)O-. In some embodiments, A9 is a bond. In some embodiments, A 10 is -OC(=O)-. In some embodiments, A 10 is -C(=O)O-. In some embodiments, A 10 is a bond. In some embodiments, A and A 10 is -OC(=O)-. In some embodiments, A and A 10 is -C(=O)O-. In some embodiments, A and A 10 is a bond. In some embodiments, A9 is -OC(=O)-, and A 10 is a bond. In some embodiments, A9 is —C(═O)O—, and A 10 is a bond.

[0223] In some embodiments, R and R are each independently C-C 24 Alkyl, -C(R6)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7). In some embodiments, R and R are each independently C-C 24 It is alkyl. In some embodiments, R is a straight chain C-C 18 It is alkyl. In some embodiments, R is a straight chain C-C 15 It is alkyl. In some embodiments, R1 is a straight chain C4-C 12 It is alkyl. In some embodiments, R1 is a straight chain C7-C alkyl, such as C7-C9 alkyl, C7-C8 alkyl, C7 alkyl, or C8 alkyl. 10 It is alkyl.

[0224] In some embodiments, R is a substituted straight chain C-C 15 Alkyl or substituted straight chain C4-C 12 Alkyl or substituted straight chain C7-C 10 alkyl, or substituted straight chain C7-C9 alkyl, or substituted straight chain C7-C8 alkyl, or substituted straight chain C7 alkyl, or substituted straight chain C8 alkyl, such as -OR b , -R a OR b , -OC(=O)R b , -C(=O)OR b , -C(=O)R b , -R a OC(=O)R b , -R aC(=O)OR b , or -R a C(=O)R b Each R is replaced by a are independently C1-C 12 alkylene, and each R b are independently H or C1-C 12 It is alkyl. In some embodiments, R1 is a branched C7-C 22 It is alkyl. In some embodiments, R is a branched C9-C 20 It is alkyl. In some embodiments, R is a branched C9-C 18 It is alkyl. In some embodiments, R is a branched C9-C 13 Alkyl, branched C 17 Alkyl, or branched C 19 Branched C9-C alkyl 17 It is alkyl.

[0225] In some embodiments, R is a substituted branched C9-C 20 Alkyl or substituted branched C9-C 18 Alkyl or substituted branched C9-C 17 Alkyl or substituted branched C9-C 13 Alkyl or substituted branched C 17 Alkyl or substituted branched C 19 alkyl, for example, -OR b , -R a OR b , -OC(=O)R b , -C(=O)OR b , -C(=O)R b , -R a OC(=O)R b , -R a C(=O)OR b , or -R a C(=O)R b Each R is replaced by a are independently C1-C 12 alkylene, and each R b are independently H or C1-C 12It is alkyl. In some embodiments, R2 is a straight chain C1-C 18 It is alkyl. In some embodiments, R2 is a straight chain C1-C 15 It is alkyl. In some embodiments, R2 is a straight chain C4-C 12 It is alkyl. In some embodiments, R2 is a straight chain C7-C alkyl, such as C7-C9 alkyl, C7-C8 alkyl, C7 alkyl, or C8 alkyl. 10 It is alkyl.

[0226] In some embodiments, R2 is a substituted straight chain C1-C 15 Alkyl or substituted straight chain C4-C 12 Alkyl or substituted straight chain C7-C 10 alkyl, or substituted straight chain C7-C9 alkyl, or substituted straight chain C7-C8 alkyl, or substituted straight chain C7 alkyl, or substituted straight chain C8 alkyl, such as -OR b , -R a OR b , -OC(=O)R b , -C(=O)OR b , -C(=O)R b , -R a OC(=O)R b , -R a C(=O)OR b , or -R a C(=O)R b Each R is replaced by a are independently C1-C 12 alkylene, and each R b are independently H or C1-C 12 It is alkyl. In some embodiments, R2 is a branched C7-C 22 It is alkyl. In some embodiments, R2 is a branched C9-C 20 It is alkyl. In some embodiments, R2 is a branched C9-C 18 It is alkyl. In some embodiments, R2 is a branched C9-C13 Alkyl, branched C 17 Alkyl, or branched C 19 Branched C9-C alkyl 17 It is alkyl.

[0227] In some embodiments, R2 is a substituted branched C9-C 20 Alkyl or substituted branched C9-C 18 Alkyl or substituted branched C9-C 17 Alkyl or substituted branched C9-C 13 Alkyl or substituted branched C 17 Alkyl or substituted branched C 19 alkyl, for example, -OR b , -R a OR b , -OC(=O)R b , -C(=O)OR b , -C(=O)R b , -R a OC(=O)R b , -R a C(=O)OR b , or -R a C(=O)R b Each R is replaced by a are independently C1-C 12アル Kiren, and each R b are independently H or C1-C 12 It is alkyl. In some embodiments, R1 is a straight chain C4-C 12 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, R1 is a straight chain C7-C 10 alkyl, and R2 is a branched C9-C 17 It is alkyl. In some embodiments, R is a branched C9-C 18 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, R is a branched C9-C 17 alkyl, and R2 is a branched C9-C 17 It is alkyl.

[0228] In some embodiments, L 11 is a bond, and the branching of R1 occurs at the α, β, or γ position of A7, for example, the branching of R1 occurs at the α position of A7: [ka] Alternatively, branching of R1 occurs at the β position of A7. [ka]

[0229] In some embodiments, L 12 is a bond, and the branching of R2 occurs at the α, β, or γ position of A8, for example, the branching of R2 occurs at the α position of A8: [ka] Alternatively, branching of R2 occurs at the β position of A8. [ka]

[0230] In some embodiments, R1 or R2 has the following structure: [ka] It is one of the following.

[0231] In some embodiments, R and R are each independently —C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7). In some embodiments, R1 and R2 are each independently -C(R6)(OR7)2, -C(R6)(SR7)2, or -C(R6)(SR7)(OR7). In some embodiments, R1 and R2 are each independently -C(H)(OR7)2, -C(H)(SR7)2, or -C(H)(SR7)(OR7).

[0232] In some embodiments, R1 is —C(R6)(OR7)2. In some embodiments, R1 is C(H)(OR7)2. In some embodiments, R2 is —C(R6)(OR7)2. In some embodiments, R2 is -C(H)(OR7)2. In some embodiments, R1 is -C(H)(SR7)2. In some embodiments, R1 is -C(H)(SR7)(OR7). In some embodiments, R2 is -C(H)(SR7)2. In some embodiments, R2 is -C(H)(SR7)(OR7). In some embodiments, R1 and R2 are -C(H)(OR7)2.

[0233] In some embodiments, R1 is -C(H)(OR7)2, -C(H)(SR7)2, or -C(H)(SR7)(OR7), and R2 is -C(H)(SR7)2 or -C(H)(SR7)(OR7). In some embodiments, R1 and R2 are -C(H)(SR7)2. In some embodiments, R1 and R2 are -C(H)(SR7)(OR7). In some embodiments, R1 is -C(H)(OR7)2 and R2 is -C(H)(SR7)2. In some embodiments, R1 is -C(H)(SR7)2 and R2 is -C(H)(SR7)2. In some embodiments, R1 is -C(H)(SR7)2 and R2 is -C(H)(SR7)(OR7). In some embodiments, R1 is -C(H)(OR7)2 and R2 is -C(H)(SR7)(OR7). In some embodiments, R and R are each independently C-C 24 alkyl or -C(R6)(OR7)2.

[0234] In some embodiments, A7 and A8 are each independently -C(=O)O- or -OC(=O)-; R1 and R2 are each independently C1-C 24 alkyl or -C(R6)(OR7)2. In some embodiments, L 11 is C1-C5 alkylene, and L 12 is C1-C5 alkylene, R1 is -C(H)(OR7)2, R2 is -C(H)(OR7)2, and R7 is C3-C 10 It is alkyl. In some embodiments, A2 is -C(=O)N(R4)- or -N(R4)C(=O)-, and R1 is a straight chain C4-C 12 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, A2 is -C(=O)N(R4)- or -N(R4)C(=O)-, and R1 is a branched C9-C 18 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, A2 is —C(═O)N(R4)— or —N(R4)C(═O)—, and L 11 is C1-C5 alkylene, and L 12 is C1-C5 alkylene, R1 is -C(H)(OR7)2 and R2 is -C(H)(OR7)2.

[0235] In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, or -OC(=O)C(=O)O-, and R1 and R2 are each independently C1-C 24 It is alkyl. In some embodiments, A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, -N(R4)C(=O)-, -N(C(=O)L 13 OR4)-, -N(C(=O)L 13 SR4)-, -N(C(=O)R4), -N(L 13 OR4)-, or -OC(=O)C(=O)O-, and R1 and R2 are each independently -C(R6)(OL 14 A 12 R7)2.

[0236] In some embodiments, A2 is -C(=O)N(R4)- or -N(R4)C(=O)-, A7 is -C(=O)O- or -OC(=O)-, A8 is -C(=O)O- or -OC(=O)-, and R1 is a straight chain C4-C 12 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, A2 is -C(=O)N(R4)- or -N(R4)C(=O)-, A7 is -C(=O)O- or -OC(=O)-, A8 is -C(=O)O- or -OC(=O)-, and R1 is a branched C9-C 18 alkyl, and R2 is a branched C9-C 18 It is alkyl. In some embodiments, A2 is —C(═O)N(R4)— or —N(R4)C(═O)—, A7 is —C(═O)O— or —OC(═O)—, A8 is —C(═O)O— or —OC(═O)—, and L 11is C1-C5 alkylene, and L 12 is C1-C5 alkylene, R1 is -C(H)(OR7)2 and R2 is -C(H)(OR7)2.

[0237] In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, A8 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and R1 and R2 are -C(H)(OR7)2. In some embodiments, A7 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, A8 is -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and R1 and R2 are -C(H)(OR7)2. In some embodiments, A7 is -C(=O)O- or -OC(=O)-, A8 is -C(=O)O- or -OC(=O)-, R1 is -C(H)(OR7)2, -C(H)(SR7)2, or -C(H)(SR7)(OR7), and R2 is -C(H)(SR7)2 or -C(H)(SR7)(OR7). In some embodiments, A7 is -SC(=O)O-, -OC(=S)O-, -C(=O)O-, or -OC(=O)S-; A8 is -OC(=S)O-, -SC(=O)O-, or -OC(=O)S-; and R1 and R2 are branched C9-C 18 It is alkyl. In some embodiments, A7 is -SC(=O)O-, -C(=O)O-, or -OC(=O)S-, A8 is -SC(=O)O- or -OC(=O)S-, and R1 and R2 are branched C9-C 18 It is alkyl.

[0238] In some embodiments, A2 is -N(R4)-, A3 is -OC(O)-, -C(O)O-, -N((R4))C(=O)-, -C(=O)N((R4))-, -OC(O)O-, -N((R4))C(=O)O-, or -OC(=O)N((R4))-, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, R1 is -C(H)(OR7)2, and R2 is -C(H)(OR7)2. In some embodiments, A2 is -N(R4)-, A3 is -OC(O)-, -C(O)O-, -N((R4))C(=O)-, -C(=O)N((R4))-, -OC(O)O-, -N((R4))C(=O)O-, or -OC(=O)N((R4))-, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, A9 and A10 are each independently -C(=O)O- or -OC(=O)-, 10 are each independently —C(═O)O— or —OC(═O)—, R1 is —C(H)(OR7)2, and R2 is —C(H)(OR7)2.

[0239] In some embodiments, each R4 is independently H or C1-C3 alkyl. In some embodiments, each R4 is independently H or C1-C2 alkyl. In some embodiments, each R4 is independently H or methyl.

[0240] In some embodiments, each R is independently C-C 12 Alkyl, or C2-C 12 Alkenyl, or C2-C 12 Alkynyl, e.g., C2-C 11 It is alkyl, C7 alkenyl, or C7 alkynyl. In some embodiments, each R7 is independently C3-C 10 It is alkyl. In some embodiments, each R7 is independently C5-C7 alkyl, for example, C6-C7 alkyl. In some embodiments, each R is independently a C-C substituted with methyl.12 It is alkyl.

[0241] In some embodiments, L1 is C1-C6 alkylene. In some embodiments, L1 is C1-C5 alkylene. In some embodiments, L1 is C1-C4 alkylene, for example, C1, C2, or C3 alkylene.

[0242] In some embodiments, L is a substituted C-C alkylene, e.g., a substituted C-C alkylene, or a substituted C, C, or C alkylene, including substituents such as —OH, —SH, halogen, O, S, N, —CN, C-C cyclohydrocarbyl, aryl, heterocyclyl ring, —R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] Examples include, but are not limited to, a are independently C1-C 12 alkylene, and each R b are independently H or C1-C12 It is alkyl.

[0243] In some embodiments, L1 is a C1-C5 alkylene substituted with hydroxyl, for example, L1 is a C2-C3 alkylene substituted with hydroxyl, for example, [ka] and its chiral structure [ka] for example, [ka] and its chiral structure [ka] is.

[0244] In some embodiments, L2 is C1-C6 alkylene. In some embodiments, L2 is C2-C5 alkylene. In some embodiments, L2 is C2-C4 alkylene. In some embodiments, L2 is a C2-C5 alkylene substituted with a substituent, e.g., a C2-C3 alkylene substituted with a substituent, the substituents being C1-C4 alkyl, -OH, -R a OC(=O)R b , or -R a C(=O)OR b are listed, and each R a are independently C1-C 12 alkylene, and each R b are independently H or C1-C 12 It is alkyl. In some embodiments, L2 is a C2-C3 alkylene substituted with methyl, e.g., L2 is a C3 alkylene substituted with methyl, e.g., [ka] is.

[0245] In some embodiments, L3 is C1-C6 alkylene. In some embodiments, L3 is a bond.

[0246] In some embodiments, L7 and L8 are each independently C1-C 14 It is alkylene. In some embodiments, L7 and L8 are each independently C1-C 10 It is alkylene. In some embodiments, L7 and L8 are each independently a C4-C8 alkylene, such as a C4-C7 alkylene, a C5-C7 alkylene, a C5 alkylene, or a C6 alkylene. In some embodiments, L7 and L8 are each independently a C1-C2 alkylene or a bond.

[0247] In some embodiments, L and L 10 are independently C1-C 14 It is alkylene. In some embodiments, L and L 10 are independently C1-C 10 It is alkylene. In some embodiments, L and L 10 are each independently a C4-C8 alkylene, such as a C4-C7 alkylene, a C5-C7 alkylene, a C5 alkylene, or a C6 alkylene. In some embodiments, L and L 10 are each independently a C4-C5 alkylene or a bond.

[0248] In some embodiments, L 11 is C1-C5 alkylene. In some embodiments, L 11 is C2-C4 alkylene, for example C3 alkylene. In some embodiments, L 11 is a bond. In some embodiments, L 12 is C1-C5 alkylene. In some embodiments, L 12 is C2-C4 alkylene, for example C3 alkylene. In some embodiments, L 12 is a bond.

[0249] In some embodiments, L 11 is a bond and L 12 is a bond. In some embodiments, L 11 is C2-C4 alkylene, and L 12 is a C2-C4 alkylene. In some embodiments, L 11 is a bond and R1 is a straight chain C4-C 12 Alkyl or branched C9-C 18 It is alkyl. In some embodiments, L 12 is a bond and R2 is a straight chain C4-C 12 Alkyl or branched C9-C 18 It is alkyl.

[0250] In some embodiments, Y1 is O, Y2 is O, R9 is -N(H)CH3, L1 is C1-C5 alkylene, A2 is -C(=O)N(R4)- or -N(R4)C(=O)-, L2 is C2-C5 alkylene, and L7 is C1-C 10 alkylene, and L8 is C1-C 10 alkylene, A7 is —C(═O)O— or —OC(═O)—, A8 is —C(═O)O— or —OC(═O)—, and L 11 is a bond and L 12 is a bond and R1 is a straight chain C4-C 12 Alkyl or branched C9-C 18 alkyl, and R2 is a straight chain C4-C 12 Alkyl or branched C9-C 18 It is alkyl. In some embodiments, Y1 is O, Y2 is O, R9 is -N(H)CH3, L1 is C1-C5 alkylene, A2 is -C(=O)N(R4)- or -N(R4)C(=O)-, L2 is C2-C5 alkylene, and L7 is C1-C 10 alkylene, and L8 is C1-C 10 alkylene, A7 is —C(═O)O— or —OC(═O)—, A8 is —C(═O)O— or —OC(═O)—, and L 11 is C2-C4 alkylene, and L 12 is C2-C4 alkylene, R1 is -C(H)(OR7)2, and R2 is -C(H)(OR7)2.

[0251] In some embodiments, Y is O, Y is O, R is —N(H)CH, L is C-C alkylene, and L is C-C 10 alkylene, and L8 is C1-C 10 alkylene, A7 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, A8 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, and L 11 is C2-C4 alkylene, and L 12 is C2-C 4アル is xylene, and R1 and R2 are -C(H)(OR7)2. In some embodiments, Y is O, Y is O, R is —N(H)CH, L is C-C alkylene, and L is C-C 10 alkylene, and L8 is C1-C 10 alkylene, A7 is —C(═O)O— or —OC(═O)—, A8 is —C(═O)O— or —OC(═O)—, and L 11 is C2-C4 alkylene, and L 12is a C2-C4 alkylene, R1 is -C(H)(OR7)2, -C(H)(SR7)2, or -C(H)(SR7)(OR7), and R2 is -C(H)(SR7)2, or -C(H)(SR7)(OR7).

[0252] In some embodiments, Y is O, Y is O, R is —N(H)CH, L is C-C alkylene, and L is C-C 10 alkylene, and L8 is C1-C 10 alkylene, A7 is -SC(=O)O-, -OC(=S)O-, -C(=O)O-, -OC(=O)-, or -OC(=O)S-, A8 is -SC(=O)O-, OC(=S)O-, or -OC(=O)S-, and L 11 and L 12 is a bond, and R1 and R2 are branched C9-C 18 It is alkyl. In some embodiments, Y is O, Y is O, R is —N(H)CH, L is C-C alkylene, and L is C-C 10 alkylene, and L8 is C1-C 10 alkylene, A7 is -SC(=O)O-, -C(=O)O-, -OC(=O)-, or -OC(=O)S-, A8 is -SC(=O)O- or -OC(=O)S-, and L 11 and L 12 is a bond, and R1 and R2 are branched C9-C 18 It is alkyl.

[0253] In some embodiments, Y is O, Y is O, R is —N(H)CH, L is C-C alkylene, each R is independently H or C-C alkyl, L is C-C alkylene, A is —OC(═O)—, —C(═O)O—, —N(R)C(═O)—, —C(═O)N(R)—, —OC(═O)O—, —N(R)C(═O)O—, or —OC(═O)N(R)—, and L is C-C 10 alkylene, and L8 is C1-C 10alkylene, A7 and A8 are each independently -C(=O)O- or -OC(=O)-, and L 11 and L 12 is a bond, R1 is —C(H)(OR7)2, and R2 is —C(H)(OR7)2. In some embodiments, Y is O, Y is O, R is —N(H)CH, L is C-C alkylene, each R is independently H or C-C alkyl, L is C-C alkylene, A is —OC(═O)—, —C(═O)O—, —N(R)C(═O)—, —C(═O)N(R)—, —OC(═O)O—, —N(R)C(═O)O—, or —OC(═O)N(R)—, L is C-C alkylene or a bond, L is C-C alkylene or a bond, A and A are each independently —C(═O)O— or —OC(═O)—, L is C-C alkylene, and L 10 is a C4-C5 alkylene, and A9 and A 10 are each independently -C(=O)O- or -OC(=O)-, and L 11 and L 12 is a bond, R1 is —C(H)(OR7)2, and R2 is —C(H)(OR7)2.

[0254] In some embodiments, in an amino lipid compound represented by formula (IV-1), (IV-3), (V-1), (V-3), (VI-1), or (VI-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, R1 and / or R2 are -C(R6)(SL 14 A 12 R7)2 or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 In some embodiments, R and R are each independently -C(R)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7. In some embodiments, in an amino lipid compound represented by formula (IV-1), (IV-3), (V-1), (V-3), (VI-1), or (VI-3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, R is C-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, A 11 R5, or -C(R6)(OL 14 A 12 R7)2, and R2 is -C(R6)(SL 14 A 12 R7)2 or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7). In some embodiments, R2 is -C(R6)(C(=O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 R7) may be R7.

[0255] In some embodiments, the present disclosure provides that A1 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -N(C(=O)R4), -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, A1 is -N(R4)-. In some embodiments, A1 is -NH-.

[0256] In some embodiments, the present disclosure provides that A2 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -N(C(=O)R4), -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0257] In some embodiments, A2 is -N(R4)-. In some embodiments, R4 is H. In some embodiments, R4 is methyl. In some embodiments, R4 is C2 alkyl, or C3 or C4 alkyl, or C5 or C6 alkyl. In some embodiments, A2 is -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)O-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -C(=O)O-, -OC(=O)-, -C(=O)S-, -SC(=O)-, -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] In some embodiments, R4 is H.

[0258] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (IA), (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V-1), (V-2), (V-3), (V-4), or (V-7) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A2 is -C(=O)N(R4)- or -N(R4)C(=O)-. In some embodiments, A2 is -C(=O)N(H)- or -N(H)C(=O)-.

[0259] In some embodiments, the present disclosure provides that A3 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -N(C(=O)R4), -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0260] In some embodiments, A3 is -N(R4)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -C(=O)O-, -OC(=O)-, [ka] In some embodiments, R4 is H. In some embodiments, R4 is methyl. In some embodiments, R4 is C2 alkyl, or C3 or C4 alkyl, or C5 or C6 alkyl.

[0261] In some embodiments, the present disclosure provides that A4 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -N(C(=O)R4), -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] The present invention provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), or (I-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0262] In some embodiments, A4 is -N(R4)-, -C(=O)N(R4)-, -N(R4)C(=O)-, [ka] in some embodiments, R4 is H. In some embodiments, R4 is methyl. In some embodiments, R4 is C2 alkyl, or C3 or C4 alkyl, or C5 or C6 alkyl.

[0263] In some embodiments, the present disclosure provides that A4 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -N(C(=O)R4), -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] The present invention provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), or (I-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0264] In some embodiments, the present disclosure provides that A5 is -N(R4)-, -C(=O)N(R4)-, -N(R4)C(=O)-, [ka] The present invention provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), or (I-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein In some embodiments, R4 is H. In some embodiments, R4 is methyl. In some embodiments, R4 is C2 alkyl, or C3 or C4 alkyl, or C5 or C6 alkyl.

[0265] In some embodiments, the present disclosure provides that A6 is -N(R4)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)S-, -SC(=O)-, -C(=O)N(R4)-, -N(R4)C(=O)-, -OC(=O)N(R4)-, -N(R4)C(=O)O-, -N(R4)C(=O)N(R4)-, -N(C(=O)R4), -OC(=O)C(=O)O-, -N(R4)C(=O)C(=O)O-, -OC(=O)C(=O)N(R4)-, -N(R4)C(=O)C(=O)N(R4)-, [ka] The present invention provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), or (I-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0266] In some embodiments, A6 is -N(R4)-, -C(=O)N(R4)-, -N(R4)C(=O)-, [ka] In some embodiments, R4 is H. In some embodiments, R4 is methyl. In some embodiments, R4 is C2 alkyl, or C3 or C4 alkyl, or C5 or C6 alkyl.

[0267] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L is C-C alkylene. In some embodiments, L1 is C4, C5, or C6 alkylene. In some embodiments, L1 is C1, C2, C3, or C4 alkylene. In some embodiments, L is C, C, or C alkylene. In some other embodiments, L is C alkylene. In some embodiments, L1 is a bond.

[0268] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), or (V-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L2 is C1-C6 alkylene or a bond. In some embodiments, L2 is C5 or C6 alkylene. In some embodiments, L2 is C1, C2, C3, or C4 alkylene. In some embodiments, L2 is a bond.

[0269] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), or (IV-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L3 is C1-C6 alkylene or a bond. In some embodiments, L3 is a C4, C5, or C6 alkylene. In some embodiments, L3 is C2 or C3 alkylene. In some embodiments, L3 is C1 alkylene, or a bond.

[0270] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), or (I-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L4 is a bond. In some other embodiments, L4 is a C4, C5, or C6 alkylene. In some other embodiments, L4 is a C2 or C3 alkylene. In some other embodiments, L4 is a C1 alkylene or a bond. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), or (I-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L5 is a bond. In some other embodiments, L5 is C4, C5, or C6 alkylene. In some other embodiments, L5 is C2 or C3 alkylene. In some other embodiments, L5 is C1 alkylene, or a bond. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), or (I-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L6 is a bond. In some other embodiments, L6 is C4, C5, or C6 alkylene. In some other embodiments, L6 is C2 or C3 alkylene. In some other embodiments, L6 is C1 alkylene, or a bond.

[0271] In some embodiments, the present disclosure provides a method for treating a cancer cell comprising administering to a patient a cancer treatment agent comprising: [ka] The present invention provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, selected from the group consisting of:

[0272] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R4 may be linked to a C atom of L1, L2, L3, L4, L5, or L6 to form a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered monocyclic or polycyclic N-atom-containing heterocyclyl ring. In some embodiments, R4 may be linked to a C atom of L1, L2, L3, L4, L5, or L6 to form a 3-, 4-, 5-, or 6-membered N-atom-containing heterocyclyl ring.

[0273] In some embodiments, one or more of -A1-L1-, -A2-L2-, -A3-L3-, -A4-L4-, -A5-L5-, or -A6-L6- is [ka] is.

[0274] In some embodiments, the present disclosure provides a method for treating L7 comprising administering any one of C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , or C 14 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , or C 14Provided is an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4), wherein R is a heteroalkylene, or a bond, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some other embodiments, L7 is C4-C 11 In some embodiments, L7 is C - In some other embodiments, L7 is a C7 or C8 alkylene. In some embodiments, L7 is a bond. In some embodiments, L7 is a C1-C4 alkylene.

[0275] In some embodiments, the present disclosure provides a method for treating a cancer comprising administering to a patient a cancer-related condition, wherein L8 is C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , or C 14 Alkylene or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O, N, or S 10 , C 11 , C 12 , C 13 , or C 14 In some embodiments, L8 is a C4-C6 heteroalkylene, or a bond. 11 In some embodiments, L is C6-C9 alkylene. In some embodiments, L is C7 or C8 alkylene. In some embodiments, L is a bond. In some embodiments, L is C1-C4 alkylene.

[0276] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A7 and A8 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, or -N(R4)C(=O)-.

[0277] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4) above, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein L is C, C, C, C, C, C, C, C, or C alkylene, or a bond. In some embodiments, L is a C-C alkylene. In some embodiments, L is a C alkylene. In some embodiments, L is a C alkylene. In some embodiments, L is a C or C alkylene. In some embodiments, L is a bond.

[0278] In some embodiments, the present disclosure provides L 10In some embodiments, L is a C1, C2, C3, C4, C5, C6, C7, or C8 alkylene, or a bond, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 10 is C-C alkylene. In some embodiments, L 10 is C alkylene. In some embodiments, L 10 is C alkylene. In some embodiments, L 10 is a C5 or C6 alkylene. In some embodiments, L 10 is a bond.

[0279] In some embodiments, the present disclosure provides A9 and A 10 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0280] In some embodiments, the present disclosure provides L 11In some embodiments, L is a C1, C2, C3, C4, C5, C6, C7, or C8 alkylene, or a bond, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 11 is C alkylene. In some embodiments, L 11 is C-C alkylene. In some embodiments, L 11 is C alkylene. In some embodiments, L 11 is a C5 or C6 alkylene. In some embodiments, L 11 is a bond.

[0281] In some embodiments, the present disclosure provides L 12 In some embodiments, L is a C1, C2, C3, C4, C5, C6, C7, or C8 alkylene, or a bond, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 12 is C alkylene. In some embodiments, L 12 is C-C alkylene. In some embodiments, L 12 is C alkylene. In some embodiments, L 12 is a C5 or C6 alkylene. In some embodiments, L 12 is a bond.

[0282] In some embodiments, the present disclosure provides that R and R are each independently a straight or 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 In some embodiments, R and R are each independently a linear or branched C8-C1 alkyl group. 20 In some embodiments, R and R are each independently a straight or branched C-C alkyl. 11 In some embodiments, R and R are each independently a straight or branched C alkyl. 15 -C 19 It is alkyl.

[0283] In some embodiments, the present disclosure provides a compound wherein R and R are each independently —C(R)(OL 14 A 12 R7)2, -C(R6)(SL 14 A 12 R7)2, or -C(R6)(SL 14 A 12 R7)(OL 14 A 12 R7), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0284] In some embodiments, the present disclosure provides a compound wherein R and R are each independently —C(R)(C(═O)OL 14 A 12 R7)2, -C(R6)(OC(=O)L 14 A 12 R7)2, -C(R6)(C(=O)OL 14 A 12 R7)R7, or -C(R6)(OC(=O)L 14 A 12 The present invention provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (VI), (VI-1), (VI-2), (VI-3), (VI-4), or (VI-5), wherein R7)R7, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0285] In some embodiments, the present disclosure provides a compound represented by formula (I) above, wherein R and R are each independently —C(R)(OR), —C(R)(SR), —C(R)(SR)(OR), —C(R)(C(═O)OR), —C(R)(OC(═O)R), —C(R)(C(═O)OR)R, or —C(R)(OC(═O)R)R. The present invention provides an amino lipid compound represented by the formula: (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0286] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (V-5), (V-5-1), (V-6), (VI), (VI-1), (VI-2), (VI-3), (VI-4), or (VI-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R is independently C, C, C, C, C, C, or C alkyl, or H. In some further embodiments, each R is independently C-C alkyl. In some embodiments, each R is H.

[0287] In some embodiments, the present disclosure provides that each L 14 are independently C1, C2, C3, C4, C5, C6, C7, or C8 alkylene, or a bond. 14 is independently a C1-C4 alkylene, or a bond. 14 are independently C1-C3 alkylene, or a bond.

[0288] In some embodiments, the present disclosure provides 12are independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)N(R4)-, or -N(R4)C(=O)-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0289] In some embodiments, the present disclosure provides that each R is independently C, C, C, C, C, C, 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 Provided are amino lipid compounds represented by formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is alkyl, alkenyl, or alkynyl, or H. In some embodiments, each R is independently C1-C4 alkyl, alkenyl, or alkynyl, or H. In some embodiments, each R is independently C2 or C3 alkyl, alkenyl, or alkynyl. In some embodiments, each R is independently C5-C6 alkyl, alkenyl, or alkynyl. 10 In some embodiments, each R is independently C 11 -C 21In some embodiments, each R is independently C 16 -C 18 In some embodiments, each R is independently: [ka] is selected from.

[0290] In some embodiments, the present disclosure provides a compound wherein R and R are each independently: [ka] [ka] The present invention provides an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (V-5), (V-5-1), (V-6), (VI), (VI-1), (VI-2), (VI-3), (VI-4), or (VI-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, selected from the group consisting of:

[0291] In some embodiments, the present disclosure provides 11 independently, C 3-6 Provided is an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4), wherein the ring is a carbocyclyl ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, each R 11 is independently C3, C4, C5, or C6 cycloalkyl, or C3, C4, C5, or C6 cycloalkenyl. In some embodiments, each R11 is independently C3-C6 cycloalkyl, for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In some embodiments, each R 11 are independently -OH, halogen, or C 1-6 C optionally substituted with substituents such as alkyl 3-6 cycloalkyl, e.g., R 11 is cyclohexyl substituted with -OH, for example, 2-hydroxycyclohexyl.

[0292] In some embodiments, the present disclosure provides 11 are independently a heterocyclyl ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0293] In some embodiments, each R 11 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring. In some embodiments, each R 11 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring containing N, O, or S. In some embodiments, each R 11 is independently a 5- or 6-membered heterocyclyl ring containing N, O, or S.

[0294] In some embodiments, the present disclosure provides 12are independently C1, C2, C3, C4, C5, or C6 alkyl. In some embodiments, each R 12 is independently C1-C3 alkyl. In some embodiments, each R 12 is independently C4-C6 alkyl.

[0295] In some embodiments, the present disclosure provides 12 are independently C2, C3, C4, C5, or C6 alkenyl. In some embodiments, each R 12 is independently C2 or C3 alkenyl. In some embodiments, each R 12 is independently C4-C6 alkenyl.

[0296] In some embodiments, the present disclosure provides 12 independently, C 3-6 Provided is an amino lipid compound represented by the above formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4), wherein the ring is a carbocyclyl ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, each R 12 is independently C3, C4, C5, or C6 cycloalkyl, or C3, C4, C5, or C6 cycloalkenyl. In some embodiments, each R 12 is independently C3-C6 cycloalkyl, for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0297] In some embodiments, each R 12 are independently -OH, halogen, or C 1-6 C optionally substituted with substituents such as alkyl 3-6 cycloalkyl, e.g., R 11 is cyclohexyl substituted with -OH, for example, 2-hydroxycyclohexyl. In some embodiments, the present disclosure provides 12 are independently a heterocyclyl ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0298] In some embodiments, each R 12 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring. In some embodiments, each R 12 is independently a 5-, 6-, 7-, or 8-membered heterocyclyl ring containing N, O, or S. In some embodiments, each R 12 is independently a 5- or 6-membered heterocyclyl ring containing N, O, or S.

[0299] In some embodiments, the present disclosure provides 12are independently H, CN, NO2, -OR, -S(O)2R, or -S(O)2N(R)2.

[0300] In some embodiments, the present disclosure provides an amino acid wherein -A1-L1-A2-, -A2-L2-A3-, -A3-L3-A4-, -A4-L4-A5-, or -A5-L5-A6- is -KQM- or -MQK-, where M is -O-, -S-, -N(R4)-, or a bond; K is -OC(=O)-, -C(=O)-, -N(R4)C(=O)-, -SC(=O)-, or a bond; and Q is a group obtained by loss of -OH from one carboxyl and loss of -H from one amino of an amino acid, wherein the moiety missing -OH from the amino acid is bonded to M. The amino acid is a compound containing an amino (-NH2 or -NH-) and a carboxyl (-COOH) in its structure, and the amino lipid compound is represented by the above formula (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (VI), (VI-1), (VI-2), (VI-3), or (VI-4), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, including naturally occurring and artificially synthesized amino lipid compounds.

[0301] For example, Q is the group obtained by losing an -OH from one carboxyl and an -H from one amino of α-alanine: [ka] where the α-alanine moiety missing the -OH is attached to M: [ka] When M is -O-, -QM- is [ka] and; When M is -S-, -QM- is [ka] and; When M is -N(R4)-, -QM- is [ka] and; When M is a bond, -QM- is [ka] and; -QM- [ka] If K is a bond, then -KQM- [ka] and when K is -OC(=O)-, -KQM- is [ka] and when K is -C(=O)-, -KQM- is [ka] and when K is -N(R4)C(=O)-, -KQM- is [ka] and when K is -SC(=O)-, -KQM- is [ka] is.

[0302] In some embodiments, in -KQM- or -MQK-, the -NH- obtained by losing one -H from the amino acid of the amino acid may be further substituted with R4. for example: [ka] In the formula, the -NH- obtained by losing one -H from the amino acid of α-alanine is further substituted with R4, [ka] It may be as follows.

[0303] In some embodiments, the amino acid has a structure represented by formula (A) or (B): [ka]

[0304] In formula (A): A a is -NH2; G is H, -OH, -SH, halogen, O, S, N, -CN, C3-C8 cyclohydrocarbyl, aryl, heterocyclyl ring, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(R b )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b, -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] is a linear C1-C6 hydrocarbylene optionally substituted with one or more substituents including:

[0305] In formula (B): A b is -NH-; G a and G b are each independently a linear C1-C5 hydrocarbylene or a bond; G a and G b the total number of C atoms is 5 or less; G c are H, -OH, -SH, halogen, O, S, N, -CN, -R b , -R a N(R b )2, -R a OR b , -R a SR b , or -R a SR b C1-C6 hydrocarbylene optionally substituted with one or more substituents, including, but not limited to: Each R a are independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenylene, C2-C containing one, two, three or more triple bonds 12 Alkynylene, C1-C containing O, N, or S 12 Heteroalkylene, C2-C containing one, two, three, or more double bonds and O, N, or S 12Heteroalkenylene or C2-C containing one, two, three or more triple bonds and O, N, or S 12 is heteroalkynylene; and Each R b are independently H, C1-C 12 Alkyl, C2-C 12 Alkenylene, C2-C 12 Alkynylene, C3-C8 cyclohydrocarbyl, C3-C8 heterocyclyl, C2-C containing one, two, three or more double bonds 12 Alkenyl, C2-C containing one, two, three or more triple bonds 12 Alkynyl, C1-C containing O, N, or S 12 Heteroalkyl, C2-C containing one, two, three, or more double bonds and O, N, or S 12 Heteroalkenyl or C2-C containing one, two, three, or more triple bonds and O, N, or S 12 It is heteroalkynyl.

[0306] In some embodiments, in the amino acid of formula (A), G is C1, C2, C3, C4, C5, or C6 alkyl, or C2, C3, C4, C5, or C6 alkenyl, or C3, C4, C5, or C6 alkynyl. In some embodiments, G is C1, C2, C3, C4, C5, or C6 alkyl. In some other embodiments, G is C1, C2, or C3 alkyl.

[0307] In some embodiments, in the amino acid of formula (A), G is a C3-C8 cyclohydrocarbyl, aryl, heterocyclyl ring, -R b , -R a N(R b )2, -R a OR b , -R a SR b , -R a OC(=O)OR b , -R a OC(=O)SR b , -R a C(=O)N(Rb )2, -OC(=O)OR b , -OC(=O)SR b , -C(=O)N(R b )2, -R a OC(=O)R b , -R a C(=O)OR b , -OC(=O)R b , -C(=O)OR b , -R a SR b ,or [ka] When substituted with one or more of a and / or R b may be linked to a C atom of G to form a monocyclic, bicyclic, or polycyclic structure. For example, G may be linked to a C atom of G to form a 5-membered monocyclic structure, such as [ka] or G is substituted with n-propyl, which is linked to the C atom of G to form a 6-membered monocyclic structure, e.g. [ka] or G is substituted with n-butyl, which is linked to the C atom of G to form a 7-membered bicyclic structure, e.g. [ka] is substituted with cyclopentyl forming

[0308] In some embodiments, in the amino acid of formula (A), G is H, —OH, —(CH2)4—NH2, —CH2—CH(CH3)2, —(CH2)2-S—CH3, —CH2-(C═O)-NH2, —(CH2)3-NH-C(═NH)-NH2, —CH2-OH, —CH(OH)-CH3, —CH3, —CH2-SH, —CH2-COOH, —(CH2)2-COOH, —(CH2)2-COOH, —CH2-C5H6, [ka] -CH(CH3)-CH2-CH3, -CH(CH3)2, [ka] -CH2-C5H5-OH, -CH2-SeH, [ka] Optionally substituted with one or more substituents including -CH2-SS-CH2-CH(NH2)-COOH, -(CH2)3-NH2, or -(CH2)3-NH-C(=O)-NH2.

[0309] In some embodiments, in the amino acid of formula (B), G a and G b are each independently C1, C2, C3, C4, or C5 alkyl, or C2, C3, C4, or C5 alkenyl, or C3, C4, or C5 alkynyl. In some embodiments, G is C1, C2, C3, C4, or C5 alkyl. In some other embodiments, G is C1, C2, or C3 alkyl. In some embodiments, in the amino acid of formula (B), G a and G b are each independently a bond.

[0310] In some embodiments, in the amino acid of formula (B), G c is a C1, C2, C3, C4, C5, or C6 hydrocarbylene optionally substituted with one or more substituents. c is a C1, C2, C3, C4, C5, or C6 alkylene optionally substituted with one or more substituents. c is a C2, C3, C4, C5, or C6 alkenyleneheteroalkyl containing 1, 2, 3, or more double bonds optionally substituted with one or more substituents. cis a C2, C3, C4, C5, or C6 alkynylenealkenylene containing one, two, three, or more triple bonds. In some embodiments, G c is a C1, C2, C3, C4, or C5 alkylene optionally substituted with one or more substituents. c is a C3, C4, or C5 alkylene optionally substituted with one or more substituents. In some embodiments, G c is a C1, C2, or C3 alkylene optionally substituted with one or more substituents, and is further a C1 or C2 alkylene optionally substituted with one or more substituents.

[0311] In some embodiments, in the amino acid of formula (B), G c is H, -OH, -(CH2)4-NH2, -CH2-CH(CH3)2, -(CH2)2-S-CH3, -CH2-(C=O)-NH2, -(CH2)3-NH-C(=NH)-N H2, -CH2-OH, -CH(OH)-CH3, -CH3, -CH2-SH, -CH2-COOH, -(CH2)2-COOH, -(CH2)2-COOH, -CH2-C5H6, [ka] -CH(CH3)-CH2-CH3, -CH(CH3)2, [ka] -CH2-C5H5-OH, -CH2-SeH, [ka] Substituted with one or more substituents including -CH2-SS-CH2-CH(NH2)-COOH, -(CH2)3-NH2, or -(CH2)3-NH-C(=O)-NH2.

[0312] In some embodiments, in the amino acid of formula (B): [ka] teeth, [ka] is selected from.

[0313] In some embodiments, suitable amino acids include, but are not limited to, glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, tyrosine, aspartic acid, histidine, asparagine, glutamic acid, lysine, glutamine, methionine, arginine, serine, threonine, cysteine, proline, selenium cysteine, pyrrolysine, cysteine, hydroxyproline, ornithine, and citrulline.

[0314] In some embodiments, Q is selected from: [ka] [ka] [ka]

[0315] In some embodiments, the present disclosure provides compounds represented by the above-described formula (I), (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (IV-5), (IV-6), (IV-7), (IV-8), (IV-9), (IV-10), (IV-11), (IV-12), (IV-13), (IV-14), (IV-15), (IV-16), (IV-17), (IV-18), (IV-19), (IV-20), (IV-21), (IV-22), (IV-23), (IV-24), (IV-25), (IV-26), (IV-27), (IV-28), (IV-29), (IV-29), (IV-21), (IV-22), (IV-23), (IV-24), (IV-25), (IV-26), (IV-27), (IV-28), (IV-29), (IV-29), (IV-29), (IV-29), (IV-30), (IV-31), (IV-32), (IV-33), (IV-34), (IV-35), (IV-36), (IV-37), (IV-38), (IV-39 ... Provided is an amino lipid compound represented by (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (V-5), (V-5-1), (V-6), (VI), (VI-1), (VI-2), (VI-3), (VI-4), (VI-5), (VII-1), (VII-1-1), (VII-2), (VII-2-1), (VII-3), or (VII-3-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0316] In some embodiments, the present disclosure provides compounds of formula (I), (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (IV-5), (IV-6), (IV-7), (IV-8), (IV-9), (IV-10), (IV-11), (IV-12), (IV-13), (IV-14), (IV-15), (IV-16), (IV-17), (IV-18), (IV-19), (IV-20), (IV-21), (IV-22), (IV-23), (IV-24), (IV-25), (IV-26), (IV-27), (IV-28), (IV-2 ... The present invention provides an amino lipid compound represented by the formula (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (V-5), (V-5-1), (V-6), (VI), (VI-1), (VI-2), (VI-3), (VI-4), (VI-5), (VII-1), (VII-1-1), (VII-2), (VII-2-1), (VII-3), or (VII-3-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0317] In some embodiments, the present disclosure provides compounds of formula (I), (I-1) above, wherein the hydrocarbyl, hydrocarbylene, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, heterohydrocarbyl, heterohydrocarbylene, carbocyclyl ring, cyclohydrocarbyl, or heterocyclyl ring is optionally substituted with one or more substituents, including, but not limited to, hydroxyl, ester group, hydrocarbyloxyl, hydrocarbyl, carbocyclyl ring, heterocyclyl ring, halogen oxygen, sulfur, amino, and amido. ), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (V-5), (V-5-1), (V-6), (VI), (VI-1), (VI-2), (VI-3), (VI-4), (VI-5), (V-7), (V-7-1), (V-7-2), (V-7-3), (VI-6), (VI-6-1), (IV-5), or (IV-5-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0318] In some embodiments, the present disclosure provides a lipid compound having the formula (I), (IA), (I-1), (I-2), (I-3), (I-4), (IV), (IV-1), (IV-2), (IV-3), (IV-4), (V), (V-1), (V-2), (V-3), (V-4), (V-5), (V-5-1), (V-5-2), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-12), (V-13), (V-14), (V-15), (V-16), (V-17), (V-18), (V-19), (V-20), (V-21), (V-22), (V-23), (V-24), (V-25), (V-26), (V-27), (V-28), (V-29 ... (VI-6-1), (VI), (VI-1), (VI-2), (VI-3), (VI-4), (VI-5), (V-7), (V-7-1), (V-7-2), (V-7-3), (VI-6), (VI-6-1), (IV-5), or (IV-5-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0319] [ka] TIFF2026502514000197.tif235170TIFF2026502514000198.tif248170TIFF2026502514000199.tif240170TIFF2026502514000200.tif243170TIFF2026502514000201.tif249170TIFF2026502514000202.tif235170TIFF2026502514000203.tif238170TIFF2026502514000204.tif248170TIFF2026502514000205.tif243170TIFF2026502514000206.tif243170TIFF2026502514000207.tif251170TIFF2026502514000208.tif251170TIFF2026502514000209.tif236170TIFF2026502514000210.tif233170TIFF2026502514000211.tif248170TIFF2026502514000212.tif222170TIFF2026502514000213.tif247170TIFF2026502514000214.tif250170TIFF2026502514000215.tif230170TIFF2026502514000216.tif239170TIFF2026502514000217.tif250170TIFF2026502514000218.tif230170TIFF2026502514000219.tif245170TIFF2026502514000220.tif241170TIFF2026502514000221.tif241170TIFF2026502514000222.tif243170TIFF2026502514000223.tif242170TIFF2026502514000224.tif247170TIFF2026502514000225.tif228170TIFF2026502514000226.tif234170TIFF2026502514000227.tif236170TIFF2026502514000228.tif231170TIFF2026502514000229.tif229170TIFF2026502514000230.tif225170TIFF2026502514000231.tif233170TIFF202650 2514000232.tif235170TIFF2026502514000233.tif230170TIFF2026502514000234.tif251170 TIFF2026502514000235.tif228170TIFF2026502514000236.tif233170TIFF2026502514000237 .tif236170TIFF2026502514000238.tif247170TIFF2026502514000239.tif240170TIFF202650 2514000240.tif243170TIFF2026502514000241.tif247170TIFF2026502514000242.tif236170 TIFF2026502514000243.tif237170TIFF2026502514000244.tif244170TIFF2026502514000245 .tif233170TIFF2026502514000246.tif232170TIFF2026502514000247.tif238170TIFF202650 2514000248.tif249170TIFF2026502514000249.tif220170TIFF2026502514000250.tif37170.

[0320] 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. 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.

[0321] 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. 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.

[0322] Within the scope 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. 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.

[0323] lipid nanoparticles 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.

[0324] 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.

[0325] 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.

[0326] 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%.

[0327] 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.

[0328] In some embodiments described above, the helper lipid is a phospholipid. Phospholipids are generally semi-synthetic and may be naturally occurring 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. In some embodiments, 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.

[0329] 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. In some embodiments, 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. In some embodiments, the structured lipid is high-purity cholesterol, particularly injectable-grade high-purity cholesterol such as CHO-HP (manufactured by AVT).

[0330] As used herein, the term PEG-lipid (polyethylene glycol-lipid) refers to a conjugate of polyethylene glycol with a lipid structure. In some embodiments, the PEG-lipid is selected from PEG-DMG and PEG-distearoylphosphatidylethanolamine (PEG-DSPE), preferably PEG-DMG. In some embodiments, the PEG-DMG is a polyethylene glycol (PEG) derivative of 1,2-dimyristoyl-sn-glycerol. In some embodiments, the PEG has an average molecular weight of about 2,000 to 5,000. In some embodiments, the PEG has an average molecular weight of about 2,000.

[0331] 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.

[0332] 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.

[0333] 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 1, Nos. 1-24, below:

[0334] [Table 1]

[0335] 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 below, numbers 25-42:

[0336] [Table 2]

[0337] As mentioned above, the lipid nanoparticles of the present disclosure can be used as active ingredient delivery vehicles. In some embodiments, the active ingredient comprises a therapeutic and / or prophylactic agent.

[0338] 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. An "effective amount" or "therapeutically effective amount" refers to the amount of the amino lipid compound of the present invention or lipid nanoparticles comprising the amino lipid 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 amino lipid 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 of ordinary skill in the art in light of their own knowledge and this disclosure.

[0339] In some embodiments, 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, e.g., 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.

[0340] In some embodiments, the biologically active moiety is a nucleic acid. 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. Lipid nanoparticles that encapsulate an active ingredient in their internal aqueous space are sometimes called "lipid nanoparticle drugs." 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). In some embodiments described above, the lipid nanoparticles of the present disclosure further comprise a nucleic acid.

[0341] In some embodiments, the mass ratio of the amino lipid compounds of the present disclosure to the 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. In some embodiments, the mass ratio of the amino lipid compounds of the present disclosure to the nucleic acid in the lipid nanoparticle is about 10: 1. 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.

[0342] 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. 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.

[0343] 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.

[0344] 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. In some embodiments, the pharmaceutical composition further comprises a buffer. In some such embodiments, the buffer is selected from phosphate buffer and Tris buffer. In some such embodiments, the buffer is a phosphate buffer. In some embodiments, the buffer has a concentration of about 5 mmol / L to about 30 mmol / L. In some embodiments, the buffer has a concentration of about 10 mmol / L. In some embodiments, the buffer has a pH of about 6 to 8. In some embodiments, the buffer has a pH of about 7 to 8, more preferably about 7 to 7.5.

[0345] In some embodiments, the pharmaceutical composition further comprises a cryoprotectant. In some such embodiments, the cryoprotectant is selected from sucrose and trehalose. In some embodiments, the cryoprotectant is sucrose. In some embodiments, the cryoprotectant has a concentration of about 50 mg / ml to 100 mg / ml. 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.

[0346] 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.

[0347] 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. In some embodiments, the cell is a mammalian cell. In some embodiments, the mammalian cell is in a mammal. As used herein, a subject is any mammal. In some embodiments, the mammal is selected from the group consisting of a mouse, rat, pig, cat, dog, horse, goat, cow, monkey, etc. In some embodiments, the subject is a human.

[0348] 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. 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.In some embodiments, the medicament is a nucleic acid pharmaceutical.In some embodiments, the pharmaceutical composition is used for the treatment and / or prevention of disease.

[0349] 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.

[0350] 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.

[0351] 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. In some embodiments, 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.

[0352] 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.

[0353] Preparation method In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (III-1) of the present disclosure, e.g., 1501-7, which can be prepared according to General Reaction Scheme 1-1 (“Method 1-1”) or General Reaction Scheme 1-2 (“Method 1-2”), wherein A1 is —N(R4)—, and R1 and R2 are —C(R6)(OL 14 A 12 R7)2.

[0354] Method 1-1: [ka] [ka] [ka] [ka] [ka]

[0355] Method 1-2: [ka] [ka]

[0356] In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (III-3) of the present disclosure, e.g., 1501-16, which can be prepared according to General Reaction Scheme 2-1 (“Method 2-1”) or General Reaction Scheme 2-2 (“Method 2-2”), wherein A1 and A4 are each independently —N(R4)—, L4 is a bond, and R1 and R2 are —C(R6)(OL 14 A 12 R7)2.

[0357] Method 2-1: [ka] [ka]

[0358] Method 2-2: [ka] [ka]

[0359] In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (III-1) of the present disclosure, e.g., 1501-20, which can be prepared according to General Reaction Scheme 3-1 (“Method 3-1”) or General Reaction Scheme 3-2 (“Method 3-2”), wherein A1 is —N(R4)—, and R1 and R2 are each independently selected from H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, or A11 It's R5.

[0360] Method 3-1: [ka] [ka] [ka]

[0361] Method 3-2: [ka] [ka]

[0362] In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (III-3) of the present disclosure, e.g., 1501-29, which can be prepared according to General Reaction Scheme 4-1 (“Method 4-1”) or General Reaction Scheme 4-2 (“Method 4-2”), wherein A1 and A4 are each independently —N(R4)—; L4 is a bond; R1 and R2 are each independently H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, or A 11 It's R5.

[0363] Method 4-1: [ka] [ka]

[0364] Method 4-2: [ka]

[0365] In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (V-3) of the present disclosure, e.g., 1501-33, which can be prepared according to general reaction scheme 5-1 (“Method 5-1”), wherein L2, L9, L 10 , A9, and A 10 is a bond, A1 is -N(R4)-, and R1 and R2 are -C(R6)(OL 14 A 12 R7)2.

[0366] Method 5-1: [ka]

[0367] In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (V-1) of the present disclosure, e.g., 1501-37, which can be prepared according to General Reaction Scheme 6-1 (“Method 6-1”), wherein L9, L 10 , A9, and A 10 is a bond, A is -N(R)-, and R and R are each independently H, C-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, or A 11 It's R5.

[0368] Method 6-1: [ka] [ka] [ka]

[0369] In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (V-3) of the present disclosure, e.g., 1501-41, which can be prepared according to General Reaction Scheme 7-1 (“Method 7-1”), wherein L2, L9, L 10 , A9, and A 10 is a bond, A is -N(R)-, and R and R are each independently H, C-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, or A 11 It's R5.

[0370] Method 7-1: [ka]

[0371] In yet another aspect, the present disclosure further provides a general synthetic method for preparing the amino lipid compounds of formula (V-1) of the present disclosure, e.g., 1501-44, which can be prepared according to General Reaction Scheme 8-1 (“Method 8-1”), wherein L9, L 10 , A9, and A 10 is a bond, A1 is -N(R4)-, and R1 and R2 are -C(R6)(OL 14 A 12 R7)2.

[0372] Method 8-1: [ka] [ka] [ka]

[0373] 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.

[0374] 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.

[0375] Beneficial effects The amino lipid compounds of the present disclosure form vehicles such as lipid nanoparticles that have excellent bioactivity and can be used to deliver bioactive ingredients, particularly water-insoluble drugs and active ingredients that are prone to degradation or decomposition (e.g., nucleic acids), thereby improving their bioavailability, immunological activity, transfection efficiency (in the case of nucleic acids), safety, and tissue and / or cellular targeting or specificity. [Example]

[0376] 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.

[0377] 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: rt room temperature, 20~30℃; 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; Pyr pyridine; TEMPO 2,2,6,6-tetramethylpiperidinoxy; NaDCC Sodium dichloroisocyanurate TBSCl tert-butyldimethylsilyl chloride TFA trifluoroacetic acid; Imid Imidazole; CPME cyclopentyl methyl ether; THF tetrahydrofuran; HOSu N-hydroxysuccinimide; DCC dicyclohexylcarbodiimide; DCE 1,2-dichloroethane; Morpholine; H time; Min minutes; TBAF·3H2O Tetrabutylammonium fluoride trihydrate; TBAF tetrabutylammonium fluoride; DEAD Diethyl azodicarboxylate; PPh3 triphenylphosphine; STAB sodium triacetoxyborohydride; MeOH methanol; EtOH ethanol; Formaldehyde.

[0378] Example 1: Synthesis of amino lipid compound 1503 Step 1: Synthesis of 1500-A [ka] Testing Procedure: 3,4-Dimethoxy-3-cyclobutene-1,2-dione (20.0 g, 140.7 mmol) and dichloromethane (1.0 L) were added to a 2 L single-neck flask, and methylamine (30% methanol solution, 15.3 g, 148 mmol) was added dropwise with stirring at room temperature. After the dropwise addition was complete, the mixture was allowed to react at room temperature for 72 hours. The mixture was then filtered, and the filter cake was washed once with water (20 mL) and once with dichloromethane (20 mL). The organic phase was separated from the filtrate, and the aqueous phase was extracted twice with dichloromethane (100 mL). The organic phases were combined, and the solvent was evaporated under reduced pressure at 40 °C to obtain the crude product. The crude product was purified by silica gel column chromatography, eluting with dichloromethane, to obtain 16.74 g of a white solid product, 1500-A, in 84.3% yield.

[0379] Step 2: Synthesis of 1501-B [ka] Testing Procedure: EDCI (36.3 g, 190.0 mmol), DMAP (1.54 g, 12.6 mmol), and dichloromethane (200 mL) were added to a 500 mL round-bottom flask and cooled to -5 °C. Pyridine (15.0 g, 190.0 mmol) was added dropwise with stirring, and after the dropwise addition was complete, the mixture was stirred at -5 °C for 10 minutes. 8-Bromooctanoic acid (33.8 g, 151.6 mmol) and 2-decanol (20.0 g, 126.4 mmol) were added. The reaction solution was then warmed to room temperature and reacted for 12 hours. The reaction was quenched by the dropwise addition of 1.0 M aqueous hydrochloric acid (100 mL), followed by two extractions with dichloromethane (150 mL), and the combined organic phases were washed with saturated aqueous sodium chloride (200 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off from the filtrate at 45°C under reduced pressure to obtain a crude product of 1501-B. The crude product was purified by silica gel column chromatography and eluted with n-hexane:ethyl acetate = 20:1 to obtain 42.8 g of a colorless oily product of 1501-B in a yield of 93.2%.

[0380] Step 3: Synthesis of 1501-C [ka] Testing Procedure: Potassium carbonate (12.2 g, 88.3 mmol) and DMF (200 mL) were added to a 500 mL round-bottom flask. Formic acid (8.67 g, 188.4 mmol) was added dropwise with stirring at room temperature. After the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour. 1501-B (42.8 g, 117.7 mmol) was added. The reaction solution was heated to 85°C and allowed to react for 8 hours. Water (1 L) was added to the reaction solution, which was then extracted twice with ethyl acetate (300 mL), and the organic phases were combined. The organic phase was washed with saturated aqueous sodium bicarbonate (200 mL) and saturated aqueous sodium chloride (200 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate by distillation under reduced pressure at 45°C to obtain crude 1501-C. The crude product was purified by silica gel column chromatography and eluted with n-hexane:ethyl acetate=20:1 to obtain 29.91 g of a colorless oily product, 1501-C, in a yield of 77.3%.

[0381] Step 4: Synthesis of 1501-D [ka] Testing Procedure: 1501-C (29.9 g, 91.1 mmol) and absolute ethanol (180 mL) were added to a 500 mL round-bottom flask. Sodium bicarbonate powder (3.06 g, 36.4 mmol) was added with stirring at room temperature, and the mixture was stirred for 3 hours. The mixture was then filtered, and the solvent was removed from the filtrate by evaporation under reduced pressure at 45 °C. Water (200 mL) was added to the residue, and the mixture was extracted twice with dichloromethane (200 mL). The organic phases were combined. The organic phases were washed with saturated aqueous sodium chloride solution (200 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate by evaporation under reduced pressure at 45 °C to give crude 1501-D. The crude product was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 10:1 to give 21.5 g of colorless oily product 1501-D in 78.6% yield.

[0382] Step 5: Synthesis of 1501-E [ka] Testing Procedure: 1501-D (21.5 g, 71.6 mmol) was added to a 500 mL single-neck flask, followed by dichloromethane (215 mL), TEMPO (223 mg, 1.43 mmol), potassium bicarbonate (5.0 g, 50.1 mmol), and sodium bromide (294 mg, 2.86 mmol). The reaction solution was cooled to 5 °C, and aqueous NaDCC solution (9.5 g, 42.9 mmol, dissolved in 85 mL of water) was added dropwise using a pressure-controlled funnel. After the dropwise addition was complete, the reaction was allowed to proceed at 5 °C for 3 h. The mixture was then filtered, and the filter cake was washed once with water (20 mL) and once with dichloromethane (20 mL). The organic phase was separated from the filtrate, and the aqueous phase was extracted twice with dichloromethane (200 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate under reduced pressure at 45°C to obtain a crude product of 1501-E, which was purified by silica gel column chromatography and eluted with dichloromethane to obtain 20.28 g of a colorless oily product of 1501-E in a yield of 94.9%.

[0383] Step 6: Synthesis of 1501-F Referring to the synthesis process of 1501-B in step 2, compound 1501-F was prepared according to the following reaction route to obtain 25.8 g of compound 1501-F with a yield of 83.0%. [ka]

[0384] Step 7: Synthesis of 1501-G Referring to the synthesis process of 1501-C in step 2, compound 1501-G was prepared according to the following reaction route to obtain 39.75 g of compound 1501-G. The crude product was used directly in the next step. [ka]

[0385] Step 8: Synthesis of 1501-H Referring to the synthesis process of 1501-D in step 4, compound 1501-H was prepared according to the following reaction route to obtain 29.3 g of compound 1501-H. The yield of the two-step reaction was 80.5%. [ka]

[0386] Step 9: Synthesis of 1501-I Referring to the synthesis process of 1501-E in step 5, compound 1501-I was prepared according to the following reaction route to obtain 22.35 g of compound 1501-I with a yield of 92.6%. [ka]

[0387] Step 10: Synthesis of 1503-A [ka] Testing Procedure: 1501-E (21.3 g, 71.4 mmol), anhydrous ethyl alcohol (210 mL), N-Boc-1,4-butanediamine (16.1 g, 85.6 mmol), and Pd / C (10%, 2.1 g) were added to a 500 mL round-bottom flask and stirred uniformly at room temperature. The mixture was then transferred to an autoclave. The autoclave was evacuated and charged with hydrogen up to 1.5 MPa, and the reaction was allowed to proceed at room temperature for 12 hours. The autoclave was then depressurized and returned to atmospheric pressure. The autoclave was opened, and the reaction solution was filtered to remove the Pd / C. The solvent was then distilled off under reduced pressure at 45 °C to obtain crude 1503-A. The crude product was purified by silica gel column chromatography, eluting with ethyl acetate:methanol = 20:1, to obtain 28.9 g of colorless oily 1503-A in 86.3% yield.

[0388] Step 11: Synthesis of 1503-B-Boc [ka] Testing Procedure: 1501-I (17.3 g, 43.5 mmol), anhydrous ethyl alcohol (140 mL), 1503-A (13.6 g, 29.0 mmol), and Pd / C (10%, 1.4 g) were added to a 500 mL round-bottom flask and stirred uniformly at room temperature. The mixture was then transferred to an autoclave. The autoclave was evacuated and charged with hydrogen up to 1.5 MPa, and the reaction was allowed to proceed at room temperature for 12 hours. The autoclave was then depressurized and returned to atmospheric pressure. The autoclave was opened, and the reaction solution was filtered to remove the Pd / C. The solvent was then distilled off under reduced pressure at 45 °C to obtain crude 1503-B-Boc. The crude product was purified by silica gel column chromatography, eluting with ethyl acetate:methanol = 20:1, to obtain 15.33 g of colorless oily 1503-B-Boc in 62.3% yield.

[0389] Step 12: Synthesis of 1503-B [ka] Testing Procedure: 1503-B-Boc (5.7 g, 6.7 mmol) and dichloromethane (50 mL) were added to a 250 mL round-bottom flask, and trifluoroacetic acid (17 mL) was slowly added while stirring at room temperature. The mixture was allowed to react for 3 hours at room temperature. The solvent was removed under reduced pressure. Ethyl acetate (50 mL) was added. The pH was adjusted to 8 with saturated sodium bicarbonate solution. The organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (100 mL). The combined organic phases were then washed with saturated aqueous sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to obtain crude 1503-B. The crude product was purified by silica gel column chromatography eluting with ethyl acetate:methanol = 20:1 to obtain 4.75 g of colorless oily 1503-B in 94.4% yield.

[0390] Step 13: Synthesis of 1503-C-Boc [ka] Testing Procedure: EDCI (575 mg, 3.0 mmol), DMAP (24 mg, 0.2 mmol), and dichloromethane (15 mL) were added to a 50 mL round-bottom flask and stirred at room temperature. Triethylamine (304 mg, 3.0 mmol) was added dropwise. After the dropwise addition was complete, the mixture was stirred at room temperature for 10 minutes. Boc-alanine (454 mg, 2.4 mmol) and 1503-B (1.5 g, 2.0 mmol) were added and the reaction was allowed to proceed at room temperature for 12 hours. The reaction mixture was quenched by adding water (20 mL) and then extracted twice with dichloromethane (20 mL). The organic phases were combined. The organic phase was then washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to give 1.7 g of crude 1503-C-Boc. This crude product was used directly in the next step of the reaction.

[0391] Step 14: Synthesis of 1503-C [ka] Testing Procedure: The crude product of 1500-C-Boc (1.7 g, 1.84 mmol) and dichloromethane (17 mL) were added to a 50 mL round-bottom flask, and trifluoroacetic acid (6 mL) was slowly added while stirring at room temperature. The reaction was allowed to proceed for 3 hours. The solvent was evaporated under reduced pressure at 45 °C. Ethyl acetate (30 mL) was added to the residue. The pH was adjusted to 8 with saturated sodium bicarbonate solution. The organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (50 mL). The combined organic phases were then washed with saturated aqueous sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was evaporated from the filtrate under reduced pressure at 45 °C to give crude product 1503-C. The crude product was purified by silica gel column chromatography eluting with ethyl acetate:methanol = 20:1 to give 0.9 g of a colorless oil, 1503-C. The yield of the two-step reaction was 55.0%.

[0392] Step 15: Synthesis of amino lipid compound 1503 [ka] Testing Procedure: 1503-C (900 mg, 1.1 mmol), dichloromethane (10 mL), and 1500-A (154 mg, 1.1 mmol) were added to a 25 mL round-bottom flask and reacted at room temperature for 72 hours. The reaction mixture was quenched by adding water (20 mL). The organic phase was separated. The aqueous phase was extracted twice with dichloromethane (20 mL), and the organic phases were combined. The organic phase was then washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to obtain crude 1503. The crude product was purified by silica gel column chromatography eluting with ethyl acetate:methanol = 10:1 to obtain 370 mg of a colorless oil, amino lipid compound 1503, in 36.3% yield and 91.25% purity. 1 H NMR (600 MHz, CDCl3) δ 8.16 (s, 1H), 8.06 (s, 1H), 7.64 (s, 1H), 4.96-4.87 (m, 2H), 3.91 (s, 2H), 3.39-3.29 (m, 5H), 3.22-3.03 (m, 6H), 2.67-2.58 (m, 2H), 2.32 (q, J = 7.3 Hz, 4H), 1.89-1.80 (m, 2H), 1.75 (s, 4H), 1.69-1.58 (m, 8H), 1.57-1.51 (m, 4H), 1.46-1.36 (m, 10H), 1.31 (dq, J = 13.8, 6.9 Hz, 38H), 1.23 (d, J = 6.2 Hz, 3H), 0.92 (t, J = 7.0 Hz, 9H). LC-MS (ESI): calculated 931.8, found (M+H): 932.3.

[0393] Example 2: Synthesis of amino lipid compound 1506 According to the method of Example 1, amino lipid compound 1506 was prepared according to the following reaction route to obtain 140 mg of amino lipid compound 1506 with a yield of 16.4% and a purity of 90.47%. [ka] 1 H NMR (600 MHz, CDCl3) δ 7.65 (s, 1H), 7.63 (s, 1H), 7.38-7.31 (m, 1H), 4.91-4.82 (m, 2H), 4.28 (t, J = 3.8 Hz, 1H), 3.73-3.69 (m, 3H), 3.32 (s, 3H), 2.48-2.34 (m, 6H), 2.27 (q, J = 7.5 Hz, 4H), 1.64-1.53 ​​(m, 5H), 1.53-1.36 (m, 15H), 1.34-1.20 (m, 48H), 1.19 (d, J = 6.2 Hz, 3H), 0.87 (t, J = 7.0 Hz, 9H). LC-MS (ESI): calculated 947.8, found (M+H): 948.2.

[0394] Example 3: Synthesis of amino lipid compound 1501 According to the method of Example 1, amino lipid compound 1501 was prepared according to the following reaction route to obtain 0.6 g of amino lipid compound 1501 with a yield of 38.7% and a purity of 92.56%. [ka] 1 H NMR (600 MHz, CDCl3) δ 8.34 (s, 1H), 7.50 (s, 1H), 7.27 (s, 1H), 4.92-4.82 (m, 2H), 4.30 (s, 2H), 3.33-3.27 (m, 5H), 2.51 (t, J = 6.1 Hz, 2H), 2.43-2.37 (m, 4H), 2.27 (q, J = 7.5 Hz, 4H), 2.02-1.82 (m, 2H), 1.70-1.63 (m, 2H), 1.63-1.54 (m, 4H), 1.56-1.45 (m, 4H), 1.45-1.38 (m, 4H), 1.34-1.22 (m, 48H), 1.19 (d, J = 6.2 Hz, 3H), 0.87 (t, J = 7.0 Hz, 9H). LC-MS (ESI): calculated 903.8, found (M+H): 904.2.

[0395] For 1500-E, compound 1500-E was prepared according to the following route, with reference to the synthesis process of 1503-B in Example 1, to obtain 980 mg of compound 1500-E with a yield of 74.0%. [ka] [ka]

[0396] Example 4: Synthesis of amino lipid compound 1502 According to the method of Example 1, amino lipid compound 1502 was prepared according to the following reaction route to obtain 0.8 g of amino lipid compound 1502 with a yield of 65.6% and a purity of 96.64%. [ka] 1 H NMR (600 MHz, CDCl3) δ 4.97-4.86 (m, 2H), 3.90 (s, 2H), 3.39-3.28 (m, 5H), 2.84 (m, 2H), 2.70 (m, 4H), 2.59-2.49 (m, 2H), 2.31 (q, J = 7.5 Hz, 4H), 1.80 (s, 2H), 1.70-1.46 (m, 14H), 1.42-1.26 (m, 48H), 1.22 (t, J = 14.9 Hz, 3H), 0.92 (t, J = 7.0 Hz, 9H). LC-MS (ESI): calculated 917.41, found (M+H): 918.1.

[0397] Example 5: Synthesis of amino lipid compound 1504 According to the method of Example 1, amino lipid compound 1504 was prepared according to the following reaction route to obtain 210 mg of amino lipid compound 1504 with a yield of 20.1% and a purity of 92.71%. [ka] 1 H NMR (600 MHz, CDCl3) δ 4.97-4.85 (m, 2H), 4.33 (s, 2H), 3.36 (m, 3H), 3.27 (dd, J = 12.0, 6.1 Hz, 2H), 2.47 (dd, J = 14.6, 7.6 Hz, 6H), 2.32 (q, J = 7.6 Hz, 4H), 1.75-1.57 (m, 8H), 1.57-1.49 (m, 6H), 1.49-1.42 (m, 4H), 1.39-1.25 (m, 48H), 1.23 (d, J = 6.2 Hz, 3H), 0.92 (t, J = 6.9 Hz, 9H). LC-MS (ESI): Calculated value 917.41, Measured value (M+H): 918.1.

[0398] Example 6: Synthesis of amino lipid compound 1505 The method of Example 1 is as follows: Amin lipid compound 1505を or less is used to prepare the reaction mixture, 980 mg of the lipid compound 1505 was obtained with a yield of 74.0% and a purity of 93.05%.

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[0399] Example 7: Synthesis of amino lipid compound 1512 Step 1: Synthesis of 1512-AT [ka] Testing Procedure: 1,4-Butanediol (20.0 g, 222 mmol) was added to a 1 L single-neck flask, followed by dichloromethane (660 mL) and imidazole (22.67 g, 333 mmol). The reaction solution was cooled to 0 °C, and TBSCl (36.7 g, 244 mmol) was added. The mixture was then reacted at 0 °C for 6 h. Saturated aqueous sodium bicarbonate (400 mL) was added. The organic phase was separated and extracted twice with dichloromethane (300 mL). The combined organic phase was then washed with saturated aqueous sodium chloride (300 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to obtain crude 1512-AT. The crude product was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 5:1 to obtain 22.5 g of colorless oily 1512-AT in 49.5% yield.

[0400] Step 2: Synthesis of 1512-AQ [ka] Testing Procedure: 1512-AT (22.5 g, 110 mmol) was added to a 1 L single-neck flask, followed by dichloromethane (300 mL), TEMPO (344 mg, 2.2 mmol), potassium bicarbonate (7.7 g, 77 mmol), and sodium bromide (453 mg, 4.4 mmol). The reaction solution was cooled to 5 °C, and aqueous NaDCC (14.5 g, 66 mmol) was added dropwise using a constant pressure funnel. After the dropwise addition was complete, the reaction was run at 5 °C for 3 h and then filtered. The filter cake was washed once with water (50 mL) and once with dichloromethane (50 mL). The organic phase was separated from the filtrate. The aqueous phase was extracted twice with dichloromethane (150 mL), and the combined organic phases were dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to give crude 1512-AQ. The crude product was purified by silica gel column chromatography eluting with dichloromethane to give 11.4 g of a colorless oily product, 1512-AQ, in a yield of 51.2%.

[0401] Step 3: Synthesis of 1512-A Synthesis of 1512-AS [ka] Testing Procedure: 1512-AQ (10.0 g, 49.4 mmol) was added to a 250 mL single-neck flask, followed by cyclopentyl methyl ether (80 mL), 1-heptanol (14.4 g, 123.5 mmol), and ammonium bromide (242 mg, 2.47 mmol). The reaction flask was equipped with a water separator and the condenser was set to 10 °C. The reaction solution was heated to 130 °C under reflux, and the water was separated. The reaction was then allowed to proceed for 6 h. The mixture was then filtered, and the solvent was removed from the filtrate by distillation under reduced pressure at 45 °C to obtain crude 1512-AS. The crude product was purified by silica gel column chromatography, eluting with n-hexane, to obtain 9.55 g of 1512-AS as a colorless oil in 46.4% yield.

[0402] Synthesis of 1512-A [ka] Testing Procedure: 1512-AS (9.55 g, 22.9 mmol) was added to a 250 mL single-neck flask, followed by tetrahydrofuran (110 mL) and TBAF (10.8 g, 34.4 mmol). The mixture was allowed to react at room temperature for 6 hours. Saturated aqueous sodium bicarbonate (80 mL) was added to the reaction solution, followed by extraction twice with ethyl acetate (80 mL). The organic phases were combined and washed with saturated aqueous sodium chloride (100 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate by distillation under reduced pressure at 45 °C to obtain crude 1512-A. The crude product was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 5:1 to obtain 6.05 g of colorless oily 1512-A in 87.4% yield.

[0403] Step 4: Synthesis of 1,8-octanedial [ka] Testing Procedure: 1,8-Octanediol (50.0 g, 342 mmol) was added to a 500 mL single-neck flask, followed by dichloromethane (700 mL), TEMPO (2.67 g, 17.1 mmol), potassium bicarbonate (51.4 g, 513 mmol), and sodium bromide (2.8 g, 27.4 mmol). After cooling the reaction solution to 5 °C, aqueous NaDCC solution (113.0 g, 513 mmol, dissolved in 500 mL of water) was added dropwise using a pressure-controlled funnel. After the dropwise addition was complete, the mixture was heated to room temperature and reacted for 12 hours. The mixture was then filtered, and the filter cake was washed once with water (30 mL) and once with dichloromethane (30 mL). The organic phase was separated from the filtrate. The aqueous phase was extracted twice with dichloromethane (500 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The solvent was distilled off from the filtrate under reduced pressure at 45°C to obtain a crude product of 1,8-octanedial. The crude product was purified by silica gel column chromatography and eluted with n-hexane:ethyl acetate = 2:1 to obtain 22.0 g of 1,8-octanedial as a yellow oil and 16.0 g of 8-oxooctanoic acid as a white solid.

[0404] Step 5: Synthesis of 8-oxooctanoic acid [ka] Testing Procedure: 1,8-Octanedial (22.0 g, 154.7 mmol) was added to a 1 L single-neck flask, followed by dichloromethane (300 mL), TEMPO (967 mg, 6.2 mmol), potassium bicarbonate (10.8 g, 108.3 mmol), and sodium bromide (1.27 g, 12.4 mmol). After cooling the reaction solution to 5 °C, aqueous NaDCC solution (20.4 g, 92.8 mmol, dissolved in 200 mL of water) was added dropwise using a pressure-controlled funnel. After the dropwise addition was complete, the mixture was heated to room temperature and reacted for 12 hours. The mixture was then filtered, and the filter cake was washed once with water (30 mL) and once with dichloromethane (30 mL). The organic phase was separated from the filtrate. The aqueous phase was extracted twice with dichloromethane (300 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate by distillation under reduced pressure at 45°C to obtain a crude product of 8-oxooctanoic acid. The crude product was purified by silica gel column chromatography and eluted with n-hexane:ethyl acetate = 2:1 to obtain 8.52 g of 8-oxooctanoic acid as a white solid. The yield of the two steps was 34.8%.

[0405] Step 6: Synthesis of 1512-CB Synthesis of 1512-B [ka] Testing Procedure: EDCI (6.75 g, 35.2 mmol), DMAP (800 mg, 7.04 mmol), and dichloromethane (70 mL) were added to a 500 mL round-bottom flask. The reaction solution was cooled to -5 °C, and pyridine (2.8 g, 35.2 mmol) was added dropwise with stirring. After the dropwise addition was complete, the mixture was stirred at -5 °C for 10 min. 8-Oxooctanoic acid (3.7 g, 23.5 mmol) and 1512-A (7.1 g, 23.5 mmol) were added, warmed to room temperature, and reacted for 8 h. The mixture was washed with saturated aqueous sodium chloride (150 mL), and the organic phase was separated. The organic phase was dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to give crude 1512-B. The crude product was purified by silica gel column chromatography and eluted with n-hexane:ethyl acetate=20:1 to obtain 5.53 g of a colorless oily product, 1512-B, in a yield of 53.2%.

[0406] Synthesis of 1512-CB [ka] Testing Procedure: Fmoc-isoserine (10.0 g, 30.55 mmol) and tetrahydrofuran (70 mL) were added to a 250 mL round-bottom flask, and HOSu (3.9 g, 33.6 mmol) and DCC (8.2 g, 39.7 mmol) were added dropwise with stirring at room temperature. Boc-propanediamine (5.3 g, 30.55 mmol), tetrahydrofuran (30 mL), and saturated sodium bicarbonate solution (20 mL) were added to another 250 mL round-bottom flask and stirred until a clear solution was obtained. The filtrate was added to the reaction solution and allowed to react at room temperature for 12 hours. Water (100 mL) was added to the reaction solution, and the mixture was extracted twice with ethyl acetate (80 mL). The organic phases were then combined. The organic phase was then washed with saturated aqueous sodium chloride solution (150 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to give crude 1512-CB. The crude product was purified by silica gel column chromatography, eluting with ethyl acetate:methanol=10:1 to give 8.0 g of 1512-CB as a white solid in 54.1% yield.

[0407] Step 7: Synthesis of 1512-C [ka] Testing Procedure: 1512-CB (8.0 g, 16.5 mmol) and dichloromethane (80 mL) were added to a 250 mL round-bottom flask, and trifluoroacetic acid (25 mL) was slowly added while stirring at room temperature. The reaction was allowed to proceed for 3 hours. The solvent was evaporated under reduced pressure at 45 °C to give crude 1512-C. The crude product was purified by silica gel column chromatography eluting with ethyl acetate:methanol = 20:1 to give 4.7 g of 1512-C as a white solid in 74.1% yield.

[0408] Step 8: Synthesis of 1512-DF [ka] Testing Procedure: 1512-C (4.7 g, 12.3 mmol), 1,2-dichloroethane (50 mL), and 1512-B (10.4 g, 24.5 mmol) were added to a 100 mL round-bottom flask and stirred at room temperature for 0.5 h. NaHB(OAc)3 (5.2 g, 24.5 mmol) was added gradually in several portions to the reaction solution, and the mixture was allowed to react at room temperature for 12 h. The solvent was evaporated under reduced pressure at 45 °C to give crude 1512-DF. The crude product was purified by silica gel column chromatography eluting with ethyl acetate:methanol = 20:1 to give 4.45 g of colorless oily 1512-DF in 29.2% yield.

[0409] Step 9: Synthesis of 1512-D [ka] Testing Procedure: 1512-DF (4.45 g, 3.6 mmol, 1.0 equiv.) and dichloromethane (50 mL) were added to a 250 mL round-bottom flask, and morpholine (25 mL) was slowly added with stirring at room temperature. The mixture was allowed to react for 12 hours at room temperature. The solvent was removed under reduced pressure, followed by extraction with ethyl acetate (100 mL) and water (100 mL). The organic phase was separated. The aqueous phase was extracted twice with ethyl acetate (100 mL), and the combined organic phases were then washed with saturated aqueous sodium chloride (100 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate under reduced pressure at 45 °C to afford crude 1512-D. The crude product was purified by column chromatography eluting with ethyl acet...

Claims

1. An amino lipid compound having the structure of formula (IA), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 1】 During the ceremony: X is C, N, or CR １３ and L １ , L ２ , L ３ , L ４ , L ５ , and L ６ are each independently C １ -C ６ Hydrocarbylene, C ３ -C ８ Carbocyclyl ring, heterocyclyl ring, C １ -C ６ heterohydrocarbylene, or a bond; L ７ , L ８ , L ９ , L １０ , L １１ , and L １２ are each independently C １ -C １８ Hydrocarbylene, C １ -C １８ heterohydrocarbylene, or a bond; A １ 、A ２ 、A ３ 、A ４ 、A ５ 、A ６ 、A ７ 、A ８ 、A ９ 、and A １０ are each independently, -N(R ４ ), -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R ４ ), -N(R ４ ),C(=O)-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R ４ ), -N(R ４ ),C(=O)O-, -N(R ４ ),C(=O)N(R ４ ), -SC(=O)N(R ４ ), -N(R ４ ),C(=O)S-, -N(C(=O)L １３ OR ４ ), -N(C(=O)L １３ SR ４ ), -N(C(=O)R ４ ), -N(L １３ OR ４ ), -N(L １３ SR ４ ), -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-, -OC(=O)C(=O)O-, -N(R ４ ),C(=O)C(=O)O-, -OC(=O)C(=O)N(R ４ ), -N(R ４ ),C(=O)C(=O)N(R ４ ), 【Chemistry 2】 or a bond; Each L １３ are independently １ -C ８ Hydrocarbylene, C １ -C ８ heterohydrocarbylene, or a bond; R １ and R ２ are each independently H, C １ -C ２４ Hydrocarbyl, C １ -C ２４ Heterohydrocarbyl, A １１ R ５ , -C(R ６ ) (OL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) ２ , or -C(R ６ ) (SL １４ A １２ R ７ ) (OL １４ A １２ R ７ ) and Each A １１ are independently —C(═O)O—, —OC(═O)—, —OC(═O)O—, —O—, —C(═O)—, —S—, —C(═O)S—, —SC(═O)—, —C(═O)N(R ４ ) -, -N(R ４ )C(=O)-, -OC(=O)N(R ４ ) -, -N(R ４ )C(=O)O-,-N(R ４ )C(=O)N(R ４ )-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -SC(=O)N(R ４ ) -, -N(R ４ )C(=O)S-, -N(C(=O)L １３ OR ４ )-,-N(C(=O)L １３ SR ４ )-,-N(C(=O)R ４ ), -N(L １３ OR ４ ) -, -N(L １３ SR ４ ) -, -N(R ４ )-, -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 benzene ring; Each A １２ are independently —C(═O)O—, —OC(═O)—, —OC(═O)O—, —O—, —C(═O)—, —S—, —C(═O)S—, —SC(═O)—, —C(═O)N(R ４ ) -, -N(R ４ )C(=O)-, -OC(=O)N(R ４ ) -, -N(R ４ )C(=O)O-,-N(R ４ )C(=O)N(R ４ )-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -SC(=O)N(R ４ ) -, -N(R ４ )C(=O)S-, -N(C(=O)L １３ OR ４ )-,-N(C(=O)L １３ SR ４ )-,-N(C(=O)R ４ ), -N(L １３ OR ４ ) -, -N(L １３ SR ４ ) -, -N(R ４ )-, -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—, a benzene ring, or a bond; Each R ４ are independently H, C １ -C ６ Hydrocarbyl, or C １ -C ６ is heterohydrocarbyl; Each R ５ are independently H, C １ -C ２４ Hydrocarbyl, or C １ -C ２４ is heterohydrocarbyl; Each R ６ are independently H, C １ -C ６ Hydrocarbyl, or C １ -C ６ is heterohydrocarbyl; Each L １４ are independently １ -C １８ Hydrocarbylene, C １ -C １８ heterohydrocarbylene, or a bond; Each R ７ are independently １ -C ２４ Hydrocarbyl or C １ -C ２４ is heterohydrocarbyl; R ３ Is, -L １５ -Z; L １５ is C １ -C １２ Hydrocarbylene, C １ -C １２ heterohydrocarbylene, or a bond; Z is H, a carbocyclic ring, a heterocyclic ring, -CN, -OR ８ , -OL １６ N(R ８ ), ２ , -C(=O)OR ８ , -C(=O)R ８ , -C(=O)SR ８ , -OC(=O)R ８ , -OC(=O)OR ８ , -OL １６ OR ８ , -N(R ８ ), ２ , -C(=O)N(R ８ ), ２ , -C(=S)N(R ８ ), ２ , -S(=O) ２ R ８ , -S(=O) ２ N(R ８ ), ２ , -OC(=O)N(R ８ ), ２ , -C(=NR ８ )N(R ８ ), ２ , -C(=NR ８ )R ８ , -C(=O)N(R ８ )OR ８ , -CH(R ８ )N(R ８ )C(=O)OR ８ , -C(R ８ ), ３ , -N(R ８ )C(=O)R ８ , -N(R ８ )C(=O)OR ８ , -N(R ８ )S(=O) ２ R ８ , -N(R ８ )C(=O)N(R ８ ), ２ , -N(R ８ )C(=S)N(R ８ ), ２ , -N(R ８ )C(=NR ８ )N(R ８ ), ２ , -N(R ８ )C(=CHR ８ )N(R ８ ) ２ 、-N(OR ８ )C(=O)R ８ 、-N(OR ８ )S(=O) ２ R ８ 、-N(OR ８ )C(=O)OR ８ 、-N(OR ８ )C(=O)N(R ８ ) ２ 、-N(OR ８ )C(=S)N(R ８ ) ２ 、-N(OR ８ )C(NR ８ )N(R ８ ) ２ 、-N(OR ８ )C(=CHR ８ )N(R ８ ) ２ 、-OP(=O)(OR ８ ) ２ 、-P(=O)(OR ８ ) ２ 、-C(=N-CN)N(R ８ ) ２ 、-C(=N-O-CH ３ )N(R ８ ) ２ 、-C(=N-SO ２ -NH ２ )N(R ８ ) ２ 、-C(=CH-NO ２ )N(R ８ ) ２ 、-C(=O)OR １１ 、-N(R ８ )R １１ 、-N(R ８ )S(=O) ２ R １１ 、-N(R ８ )C(=NR １２ )N(R ８ ) ２ 、-N(R ８ )C(=CHR １２ )N(R ８ ) ２ 、-N(OR ８ )C(=NR １２ ) N (R ８ ) ２ , -N(OR ８ ) C(=CHR １２ ) N (R ８ ) ２ , -C(=NR １２ ) N (R ８ ) ２ , -C(=NR １２ ) R ８ , or -C(R ８ ) N (R ８ ) ２ C(=O)OR ８ and Each R ８ are independently hydrogen or C １ -C １２ alkyl or C containing one, two, three or more double bonds ２ -C １２ alkenyl or C containing one, two, three or more triple bonds ２ -C １２ Alkynyl, or C １ -C １２ Heteroalkyl or C containing 1, 2, 3 or more double bonds ２ -C １２ heteroalkenyl or C containing one, two, three or more triple bonds ２ -C １２ is heteroalkynyl; Each R １１ are independently ３－６ is a carbocyclyl ring or a heterocyclyl ring; Each R １２ are independently H, CN, NO ２ , C １－６ Alkyl, —OR, —S(O) ２ R, -S(O) ２ N (R) ２ , C ２－６ Alkenyl, C ３－６ is a carbocyclyl ring or a heterocyclyl ring; Each L １６ are independently １ -C １８ Hydrocarbylene, C １ -C １８ heterohydrocarbylene, or a bond; R １３ is H, C １ -C ６ Hydrocarbyl or C containing O, N, or S １ -C ６ It is a heterohydrocarbyl.

2. R １ and R ２ Further, each independently represents -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) ２ , -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) ２ , -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) R ７ , or -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) R ７ 2. The amino lipid compound of claim 1, wherein:

3. Z is, 【Transformation 3】 and In the formula, Y １ and Y ２ are each independently O or S; Each R ９ are independently H, halogen, —R ｂ , -N(R ｂ ) ２ , -CN, -N ３ , -C(=O)OR ｂ , —OC(═O)R ｂ , -OR ｂ , -SR ｂ , -S(-O)R ｂ , -S(=O)OR ｂ , -S(=O) ２ OR ｂ , -N(R ｂ ) ２ , -N(R ｂ ) S(=O) ２ R ｂ , -NHR ａ N (R ｂ ) ２ , -NHR ａ OR ａ N (R ｂ ) ２ , -NHR ａ OR ｂ , or -N(R ａ OR ｂ ) ２ and Each R ａ are independently １ -C １２ Alkylene, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenylene, C containing one, two, three or more triple bonds ２ -C １２ Alkynylene, C containing O, N, or S １ -C １２ Heteroalkylene, C containing 1, 2, 3 or more double bonds and O, N, or S ２ -C １２ heteroalkenylene or C containing one, two, three or more triple bonds and O, N, or S; ２ -C １２ heteroalkynylene; Each R ｂ are independently H, C １ -C １２ Alkyl, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenyl, C containing 1, 2, 3 or more triple bonds ２ -C １２ Alkynyl, C containing O, N, or S １ -C １２ Heteroalkyl, C containing one, two, three or more double bonds and O, N, or S ２ -C １２ heteroalkenyl or C containing one, two, three or more triple bonds and O, N, or S ２ -C １２ heteroalkynyl, 3. The amino lipid compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

4. Z is, 【Chemistry 4】 The amino lipid compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

5. A ２ が、-N(R ４ )-、-C(=O)O-、-OC(=O)-、-OC(=O)O-、-O-、-C(=O)-、-S-、-C(=O)S-、-SC(=O)-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-OC(=O)S-、-SC(=O)O-、-SC(=O)S-、-OC(=O)N(R ４ )-、-N(R ４ )C(=O)O-、-N(R ４ )C(=O)N(R ４ )-、-SC(=O)N(R ４ )-、-N(R ４ )C(=O)S-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-N(L １３ SR ４ )-、-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-、-OC(=O)C(=O)O-、-N(R ４ )C(=O)C(=O)O-、-OC(=O)C(=O)N(R ４ )-、-N(R ４ )C(=O)C(=O)N(R ４ )-、 【Transformation 5】 5. The amino lipid compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

6. L １５ The amino lipid compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

7. A １ -N (R ４ 7. The amino lipid compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

8. A １ The amino lipid compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein is -NH-.

9. The amino lipid compound according to any one of claims 1 to 8, wherein the amino lipid compound has a structure represented by formula (V-2), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 【Transformation 6】

10. The amino lipid compound according to any one of claims 1 to 3, wherein the amino lipid compound has a structure represented by formula (V-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Transformation 7】 In the formula, R １ and R ２ are each independently C １ -C ２４ Hydrocarbyl, —C(R ６ ) (OL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) (OL １４ A １２ R ７ ), -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) ２ , -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) ２ , -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) R ７ , or -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) R ７ is.

11. The amino lipid compound according to claim 10, wherein the amino lipid compound has a structure represented by formula (V-5-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 【Transformation 8】

12. Y １ and Y ２ are each independently O or S; R ９ is H, halogen, -R ｂ , -N(R ｂ ) ２ , -CN, -N ３ , -C(=O)OR ｂ , —OC(═O)R ｂ , -OR ｂ , -SR ｂ , -S(-O)R ｂ , -S(=O)OR ｂ , -S(=O) ２ OR ｂ , -N(R ｂ ) S(=O) ２ R ｂ , -NHR ａ N (R ｂ ) ２ , -NHR ａ OR ａ N (R ｂ ) ２ , -NHR ａ OR ｂ , or -N(R ａ OR ｂ ) ２ and Each R ａ But independently, C １ -C １２ Alkylene, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenylene, C containing one, two, three or more triple bonds ２ -C １２ Alkynylene, C containing O, N, or S １ -C １２ Heteroalkylene, C containing 1, 2, 3 or more double bonds and O, N, or S ２ -C １２ heteroalkenylene or C containing one, two, three or more triple bonds and O, N, or S; ２ -C １２ heteroalkynylene; Each R ｂ However, independently, H, C １ -C １２ Alkyl, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenyl, C containing 1, 2, 3 or more triple bonds ２ -C １２ Alkynyl, C containing O, N, or S １ -C １２ Heteroalkyl, C containing one, two, three or more double bonds and O, N, or S ２ -C １２ heteroalkenyl or C containing one, two, three or more triple bonds and O, N, or S ２ -C １２ is heteroalkynyl; L １ is C １ -C ６ Hydrocarbylene, C ３ -C ８ Carbocyclyl ring, or C １ -C ６ heterohydrocarbylene; L ７ and L ８ However, each independently, C １ -C １０ is hydrocarbylene; L １１ and L １２ However, each independently, C １ -C ５ is a hydrocarbylene or bond; A ７ が-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 9】 and A ８ が-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 10】 or a bond; R １ and R ２ However, each independently, C １ -C ２４ alkyl, —C(R ６ ) (OR ７ ) ２ , -C(R ６ ) (SR ７ ) ２ , or -C(R ６ ) (SR ７ ) (OR ７ ) and Each R ７ But independently, C １ -C １２ is a hydrocarbyl; L ９ , L １０ , A ９ , and A １０ is a bond, 12. The amino lipid compound of claim 10 or 11, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

13. L ９ , L １０ , A ９ , and A １０ is a bond, and A ７ and A ８ are each independently —C(═O)O— or —OC(═O)—, and R １ and R ２ -C(H)(OR ７ ) ２ 13. The amino lipid compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

14. L ９ , L １０ , L １１ , and L １２ is a bond, and A ７ is —C(═O)O— or —OC(═O)—, and A ８ is —C(═O)O— or —OC(═O)—, and A ９ and A １０ is a bond, and R １ and R ２ However, each independently, C １ -C ２４ 13. The amino lipid compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

15. The amino lipid compound according to any one of claims 1 to 3, wherein the amino lipid compound has a structure represented by formula (V-6), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 11】 In the formula, R １ and R ２ are each independently -C(R ６ ) (SL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) (OL １４ A １２ R ７ ), -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) ２ , -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) ２ , -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) R ７ , or -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) R ７ is.

16. L １ is C １ -C ６ Hydrocarbylene or C １ -C ６ heterohydrocarbylene; L １５ is C １ -C ２ is hydrocarbylene; L ７ and L ８ However, each independently, C １ -C １０ is hydrocarbylene; L １１ and L １２ are each independently C １ -C ５ is hydrocarbylene; A ７ が-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 12】 and A ８ が-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 13】 or a bond; R １ and R ２ are each independently -C(R ６ ) (C(=O)OR ７ ) ２ , -C(R ６ ) (OC(=O)R ７ ) ２ , -C(R ６ ) (C(=O)OR ７ ) R ７ , or -C(R ６ ) (OC(=O)R ７ ) R ７ and Each R ７ But independently, C １ -C １２ is a hydrocarbyl, 16. The amino lipid compound of claim 15, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

17. The amino lipid compound according to any one of claims 1 to 3, wherein the amino lipid compound has a structure represented by formula (V-7), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 14】 During the ceremony: Y １ and Y ２ are each independently O or S; Each R ９ are independently H, halogen, —R ｂ , -N(R ｂ ) ２ , -CN, -N ３ , -C(=O)OR ｂ , —OC(═O)R ｂ , -OR ｂ , -SR ｂ , -S(-O)R ｂ , -S(=O)OR ｂ , -S(=O) ２ OR ｂ , -N(R ｂ ) S(=O) ２ R ｂ , -NHR ａ N (R ｂ ) ２ , -NHR ａ OR ａ N (R ｂ ) ２ , -NHR ａ OR ｂ , or -N(R ａ OR ｂ ) ２ and Each R ａ are independently １ -C １２ Alkylene, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenylene, C containing one, two, three or more triple bonds ２ -C １２ Alkynylene, C containing O, N, or S １ -C １２ Heteroalkylene, C containing 1, 2, 3 or more double bonds and O, N, or S ２ -C １２ heteroalkenylene or C containing one, two, three or more triple bonds and O, N, or S; ２ -C １２ heteroalkynylene; Each R ｂ are independently H, C １ -C １２ Alkyl, C ２ -C １２ Alkenyl, C ２ -C １２ Alkynyl, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenylheteroalkyl, C containing 1, 2, 3 or more triple bonds ２ -C １２ Alkynylheteroalkyl, C containing O, N, or S １ -C １２ Heteroalkyl, C containing one, two, three or more double bonds and O, N, or S ２ -C １２ heteroalkenyl or C containing one, two, three or more triple bonds and O, N, or S ２ -C １２ is heteroalkynyl; L １ and L ２ are each independently C １ -C ６ Hydrocarbylene, C ３ -C ８ Carbocyclyl ring, or C １ -C ６ heterohydrocarbylene; L ７ and L ８ are each independently C １ -C １０ is hydrocarbylene; L １１ and L １２ are each independently C １ -C ５ is a hydrocarbylene or bond; A ２ and A ７ are each independently, -N(R ４ ), -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R ４ ), -N(R ４ ), -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OC(=O)N(R ４ ), -N(R ４ ), -N(R ４ ), -N(R ４ ), -SC(=O)N(R ４ ), -N(R ４ ), -N(C(=O)L １３ OR ４ ), -N(C(=O)L １３ SR ４ ), -N(C(=O)R ４ ), -N(L １３ OR ４ ), -N(L[[ID=�7]] １３ SR ４ ), -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-, -OC(=O)C(=O)O-, -N(R ４ ), -OC(=O)C(=O)N(R ４ ), -N(R ４ ), -N(R ４ ), 【Chemistry 15】 and R １ and R ２ are each independently C １ -C ２４ Hydrocarbyl, —C(R ６ ) (OL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) (OL １４ A １２ R ７ ), -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) ２ , -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) ２ , -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) R ７ , or -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) R ７ and Each R ７ are independently １ -C １２ It is a hydrocarbyl.

18. The amino lipid compound according to claim 17, wherein the amino lipid compound has a structure represented by formula (V-7-1) or (V-7-2), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 16】 During the ceremony: A ７ は-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 17】 and A ８ は-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 [Chemistry 18] or a bond; R １ and R ２ are each independently C １ -C ２４ alkyl, —C(R ６ ) (OR ７ ) ２ , -C(R ６ ) (SR ７ ) ２ , or -C(R ６ ) (SR ７ ) (OR ７ )

19. The amino lipid compound according to any one of claims 1 to 3, wherein the amino lipid compound has a structure represented by formula (VI-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 19】 In the formula, R １ and R ２ are each independently C １ -C ２４ Hydrocarbyl, —C(R ６ ) (OL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) ２ , -C(R ６ ) (SL １４ A １２ R ７ ) (OL １４ A １２ R ７ ), -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) ２ , -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) ２ , -C(R ６ ) (C(=O)OL １４ A １２ R ７ ) R ７ , or -C(R ６ ) (OC(=O)L １４ A １２ R ７ ) R ７ is.

20. L １５ is C １ -C ２ is hydrocarbylene; R ４ is C １ -C ６ Hydrocarbyl or C １ -C ６ is heterohydrocarbyl; L ７ and L ８ However, each independently, C １ -C １０ is hydrocarbylene; L １１ and L １２ However, each independently, C １ -C ５ is hydrocarbylene; A ７ が、-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 20】 and A ８ が、-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 21】 or a bond; R １ and R ２ are each independently -C(R ６ ) (OR ７ ) ２ , -C(R ６ ) (SR ７ ) ２ , or -C(R ６ ) (SR ７ ) (OR ７ ) and Each R ７ But independently, C １ -C １２ is a hydrocarbyl, 20. The amino lipid compound of claim 19, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

21. A ７ and A ８ is —C(═O)O—, and L ７ and L ８ However, each independently, C ４ -C ８ alkylene, and R １ and R ２ -C(H)(OR ７ ) ２ 21. The amino lipid compound according to any one of claims 1 to 8, 19, and 20, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

22. L １５ is C １ 22. The amino lipid compound of any one of claims 1 to 8, 19, and 21, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

23. The amino lipid compound according to any one of claims 1 to 3, wherein the amino lipid compound has a structure represented by formula (VI-6), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 22】 During the ceremony: Y １ and Y ２ are each independently O or S; Each R ９ are independently H, halogen, —R ｂ , -N(R ｂ ) ２ , -CN, -N ３ , -C(=O)OR ｂ , —OC(═O)R ｂ , -OR ｂ , -SR ｂ , -S(-O)R ｂ , -S(=O)OR ｂ , -S(=O) ２ OR ｂ , -N(R ｂ ) S(=O) ２ R ｂ , -NHR ａ N (R ｂ ) ２ , -NHR ａ OR ａ N (R ｂ ) ２ , -NHR ａ OR ｂ , or -N(R ａ OR ｂ ) ２ and Each R ａ are independently １ -C １２ Alkylene, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenylene, C containing one, two, three or more triple bonds ２ -C １２ Alkynylene, C containing O, N, or S １ -C １２ Heteroalkylene, C containing 1, 2, 3 or more double bonds and O, N, or S ２ -C １２ heteroalkenylene or C containing one, two, three or more triple bonds and O, N, or S; ２ -C １２ heteroalkynylene; Each R ｂ are independently H, C １ -C １２ Alkyl, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenyl, C containing 1, 2, 3 or more triple bonds ２ -C １２ Alkynyl, C containing O, N, or S １ -C １２ Heteroalkyl, C containing one, two, three or more double bonds and O, N, or S ２ -C １２ heteroalkenyl or C containing one, two, three or more triple bonds and O, N, or S ２ -C １２ is heteroalkynyl; L １ is C １ -C ６ Hydrocarbylene, C ３ -C ８ Carbocyclyl ring, or C １ -C ６ heterohydrocarbylene; L ７ and L ８ are each independently C １ -C １０ is hydrocarbylene; L １１ and L １２ are each independently C １ -C ５ is a hydrocarbylene or bond; A ７ , A ８ , R １ , and R ２ is one selected from the following: (1) R １ and R ２ are each independently -C(R ６ ) (OR ７ ) ２ , -C(R ６ ) (SR ７ ) ２ , or -C(R ６ ) (SR ７ ) (OR ７ ) and A ７ and A ８ are each independently —C(═O)O—, —OC(═O)—, —OC(═O)O—, —OC(═O)C(═O)O—, —O—, —SC(═O)O—, —OC(═O)S—, —C(═O)N(R ４ ) - or -N(R ４ )C(═O)—; (2) R １ and R ２ are each independently C １ -C ２４ A is a hydrocarbyl; ７ is —OC(═O)S— or —SC(═O)O—; A ８ -C(=O)O-, -OC(=O)-, -OC(=O)O-, -O-, -SC(=O)O-, -OC(=O)S-, -C(=O)N(R ４ ) -, -N(R ４ )C(=O)-, or -OC(=O)C(=O)O-; and (3) R １ and R ２ are each independently C １ -C ２４ is hydrocarbyl; and A ７ and A ８ are each --OC(.dbd.S)O--.

24. The amino lipid compound according to any one of claims 1 to 3, wherein the amino lipid compound has a structure represented by formula (IV-5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 23】 During the ceremony: Y １ and Y ２ are each independently O or S; Each R ９ are independently H, halogen, —R ｂ , -N(R ｂ ) ２ , -CN, -N ３ , -C(=O)OR ｂ , —OC(═O)R ｂ , -OR ｂ , -SR ｂ , -S(-O)R ｂ , -S(=O)OR ｂ , -S(=O) ２ OR ｂ , -N(R ｂ ) S(=O) ２ R ｂ , -NHR ａ N (R ｂ ) ２ , -NHR ａ OR ａ N (R ｂ ) ２ , -NHR ａ OR ｂ , or -N(R ａ OR ｂ ) ２ and Each R ａ are independently １ -C １２ Alkylene, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenylene, C containing one, two, three or more triple bonds ２ -C １２ Alkynylene, C containing O, N, or S １ -C １２ Heteroalkylene, C containing 1, 2, 3 or more double bonds and O, N, or S ２ -C １２ heteroalkenylene or C containing one, two, three or more triple bonds and O, N, or S; ２ -C １２ heteroalkynylene; Each R ｂ are independently H, C １ -C １２ Alkyl, C ２ -C １２ Alkenylene, C ２ -C １２ Alkynylene, C ３ -C ８ Cyclohydrocarbyl, C ３ -C ８ Heterocyclyl, C containing one, two, three or more double bonds ２ -C １２ Alkenyl, C containing 1, 2, 3 or more triple bonds ２ -C １２ Alkynyl, C containing O, N, or S １ -C １２ Heteroalkyl, C containing one, two, three or more double bonds and O, N, or S ２ -C １２ heteroalkenyl or C containing one, two, three or more triple bonds and O, N, or S ２ -C １２ is heteroalkynyl; L １ and L ２ are each independently C １ -C ６ is hydrocarbylene; L ３ is C １ -C ６ is a hydrocarbylene or bond; L ７ and L ８ are each independently C １ -C １０ is a hydrocarbylene or bond; L １１ and L １２ are each independently C １ -C ５ is a hydrocarbylene or bond; A ３ は、-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-OC(=O)N(R ４ )-、-N(R ４ )C(=O)O-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、-N(R ４ )C(=O)C(=O)O-、-OC(=O)C(=O)N(R ４ )-、-N(R ４ )C(=O)C(=O)N(R ４ )-、 【Chemistry 24】 and A ７ は、-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 25】 and A ８ は、-C(=O)O-、-OC(=O)-、-OC(=O)O-、-C(=O)N(R ４ )-、-N(R ４ )C(=O)-、-N(C(=O)L １３ OR ４ )-、-N(C(=O)L １３ SR ４ )-、-N(C(=O)R ４ )、-N(L １３ OR ４ )-、-OC(=O)C(=O)O-、 【Chemistry 26】 or a bond; R １ and R ２ are each independently C １ -C ２４ alkyl, —C(R ６ ) (OR ７ ) ２ , -C(R ６ ) (SR ７ ) ２ , or -C(R ６ ) (SR ７ ) (OR ７ )

25. The amino lipid compound of claim 24, wherein the amino lipid compound has a structure represented by formula (IV-5-1), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 27】 In the formula, R １ and R ２ are each independently -C(R ６ ) (OR ７ ) ２ is.

26. _ ７ および! ８ が、それぞ,C(!!Q、!!(( [. ４ )?、!((() ４ Pi １３ _) ４ )?、!((=))) １３ 32 ４ )?、(((M)) ４ )、(() １３ _) ４ 、、!C(!)C(B)﯁m、 【Chemistry 28】 That is, 20. The amino lipid compound according to any one of claims 1 to 11, 15, 17, and 19, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

27. A ７ and A ８ are each independently —C(═O)O—, —OC(═O)—, —OC(═O)O—, —C(═O)N(R ４ ) -, -N(R ４ 27. The amino lipid compound of any one of claims 1 to 12, 15 to 20, and 24 to 26, wherein the amino lipid compound is -OC(=O)C(=O)-, or -OC(=O)C(=O)O-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

28. A ７ and A ８ are each independently -C(=O)O- or -OC(=O)-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

29. A ７ and A ８ 29. The amino lipid compound of claim 28, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

30. A ７ and A ８ are each independently —C(═O)O— or —OC(═O)—, and L １１ is a bond, and L １２ is a bond, and R １ and R ２ are each independently a linear C ４ -C １２ Alkyl or branched C ９ -C １８ 25. The amino lipid compound of any one of claims 12, 18, 23, and 24, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

31. A ７ and A ８ are each independently —C(═O)O— or —OC(═O)—, and R １ and R ２ are each independently —C(H)(OR ７ ) ２ 26. The amino lipid compound according to any one of claims 12, 18, 20, and 23 to 25, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

32. R １ and R ２ However, each independently, C １ -C ２４ 30. The amino lipid compound according to any one of claims 1, 3 to 12, 17 to 19, 23, 24, and 26 to 29, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

33. R １ is a linear C ４ -C １２ alkyl, and R ２ Branch C ９ -C １８ 33. The amino lipid compound of claim 30 or 32, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

34. R １ is a linear C ７ -C １０ alkyl, and R ２ Branch C ９ -C １７ 33. The amino lipid compound of claim 30 or 32, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

35. R １ Branch C ９ -C １８ alkyl, and R ２ Branch C ９ -C １８ 33. The amino lipid compound of claim 30 or 32, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

36. R １ Branch C ９ -C １７ alkyl, and R ２ Branch C ９ -C １７ 33. The amino lipid compound of claim 30 or 32, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

37. R １ and R ２ are each independently —C(H)(OR ７ ) ２ 30. The amino lipid compound according to any one of claims 1, 3 to 12, and 17 to 29, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

38. Each R ７ But independently, C ３ -C １０ 40. The amino lipid compound of claim 31 or 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

39. Each R ７ are independently linear C ５ -C ７ 40. The amino lipid compound of claim 31 or 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

40. Y １ and Y ２ is O, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

41. R ９ -N (R ｂ ) ２ 41. The amino lipid compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

42. Each R ｂ However, independently, H, C １ -C ６ Alkyl, or C ２ -C ３ 42. The amino lipid compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkenyl.

43. R ９ -N(H)CH ３ 43. The amino lipid compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

44. L １ is C １ -C ５ 44. The amino lipid compound of any one of claims 1 to 18 and 23 to 43, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

45. L １ is C ２ -C ５ 44. The amino lipid compound of any one of claims 1 to 16 and 26 to 43, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

46. L １ is substituted with a substituent １ -C ５ C substituted with alkylene or substituent ２ -C ５ 46. ​​The amino lipid compound of claim 44 or 45, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

47. L ２ is C ２ -C ４ 47. The amino lipid compound of any one of claims 1 to 3, 17, 18, and 24 to 46, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

48. L ７ and L ８ However, each independently, C ４ -C ８ 48. The amino lipid compound of any one of claims 1 to 47, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

49. L １１ is C ２ -C ４ 49. The amino lipid compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

50. L １２ is C ２ -C ４ 50. The amino lipid compound of any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

51. Each R ４ are independently H or C １ -C ２ 51. The amino lipid compound of any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

52. 52. The amino lipid compound of any one of claims 1 to 51, having one of the following structures: 【Chemistry 29】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】

53. A lipid nanoparticle comprising the amino lipid compound of any one of claims 1 to 52.

54. 54. A pharmaceutical composition comprising the amino lipid compound of any one of claims 1 to 52 or the lipid nanoparticle of claim 53, and a pharmaceutically acceptable carrier, diluent, or excipient.

55. Use of the amino lipid compound of any one of claims 1 to 52 in the manufacture of a vehicle for an active ingredient.

56. 55. Use of an amino lipid compound according to any one of claims 1 to 52, a lipid nanoparticle according to claim 53, or a pharmaceutical composition according to claim 54 in the manufacture of a medicament.

57. Use of the amino lipid compound of any one of claims 1 to 52, the lipid nanoparticle of claim 53, or the pharmaceutical composition of claim 54 in the manufacture of a pharmaceutical for nucleic acid introduction.

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