Amino lipid compounds and lipid nanoparticles for delivery of bioactive ingredients

Abstract

Provided are an amino lipid compound for preparing a lipid nanoparticle for delivering an active ingredient and a method for preparing the same, a lipid nanoparticle and a pharmaceutical composition containing the amino lipid compound, and uses thereof.

Description

Amino lipid compounds and lipid nanoparticles for delivery of bioactive ingredients Technical Field

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

[0002] The safe and effective targeted delivery of bioactive ingredients (such as nucleic acids, proteins, and small molecule drugs) to cells, tissues, and / or organs has always been a technical challenge in the field of drug delivery, especially for nucleic acid drugs, which are easily degraded by nucleases in plasma. Nucleic acid drugs, including mRNA, antisense oligonucleotides (ASOs), microRNA (miRNA), small interfering RNA (siRNA), and aptamers, are gradually being developed as a new type of treatment, with great therapeutic potential in areas such as cancer treatment, infectious disease prevention, and genetic disease treatment.

[0003] The delivery of nucleic acid drugs via lipid nanoparticles has been widely used. However, the targeting, safety, and delivery efficiency of nucleic acid drug delivery still need to be improved. Different nucleic acid drugs, cells (or tissues, organs), and application scenarios all require lipid nanoparticles with different properties to match. Therefore, to meet the delivery needs of different nucleic acid drug application scenarios, there is a huge demand for the development of different lipid nanoparticles, especially amino lipid compounds for the configuration of lipid nanoparticles.

[0004] Summary of the Invention

[0005] One aspect of the present disclosure provides an amino lipid compound represented by formula (I):

[0006] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1 and R2 are each as defined below.

[0007] Another aspect of the present disclosure provides a method for preparing the amino lipid compound.

[0008] Another aspect of the present disclosure provides use of the amino lipid compound for preparing a delivery vehicle for an active ingredient.

[0009] Another aspect of the present disclosure provides lipid nanoparticles containing the amino lipid compound.

[0010] Another aspect of the present disclosure provides a pharmaceutical composition containing the lipid nanoparticles.

[0011] Another aspect of the present disclosure provides a method for delivering a bioactive ingredient to a cell, tissue or organ via the lipid nanoparticle or pharmaceutical composition.

[0012] Another aspect of the present disclosure provides a method for producing a polypeptide and / or protein of interest in mammalian cells by using the lipid nanoparticle or pharmaceutical composition.

[0013] Another aspect of the present disclosure provides use of the amino lipid compound, lipid nanoparticle or pharmaceutical composition in preparing a medicament.

[0014] Another aspect of the present disclosure provides a method for preventing and / or treating a disease or disorder in a mammal in need thereof by using the lipid nanoparticle or pharmaceutical composition.

[0015] Another aspect of the present disclosure provides use of the amino lipid compound, lipid nanoparticle or pharmaceutical composition in preparing a medicament for nucleic acid transfer. DETAILED DESCRIPTION

[0016] definition

[0017] Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as those commonly understood by those skilled in the art. Reference to the technology used herein refers to the technology commonly understood in the art, including those changes in technology or equivalent technology substitutions that are obvious to those skilled in the art. Although it is believed that the following terms are well understood by those skilled in the art, the following definitions are still set forth to better explain the present invention.

[0018] As used herein, the terms "comprises," "comprising," "having," "containing," or "involving," and variations thereof herein, are inclusive or open-ended and do not exclude additional unrecited elements or method steps.

[0019] The term "hydrocarbyl" as used herein means the group remaining after an aliphatic hydrocarbon loses one hydrogen atom, including straight-chain or branched, saturated or unsaturated hydrocarbon groups. Hydrocarbyl groups include, but are not limited to, alkyl, alkenyl, and alkynyl. Preferably, the hydrocarbon group has 1 to 24 carbon atoms (C1-C 24 hydrocarbon radicals), for example, having 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 、C23 or C 24 Examples of hydrocarbon groups include, but are not limited to, C1-C 24 Hydrocarbon, C1-C 22 Hydrocarbon, C1-C 20 Hydrocarbon, C1-C 18 Hydrocarbon, C1-C 16 Hydrocarbon, C1-C 12 Hydrocarbon, C1-C 10 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, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl and C8 alkyl. Unless otherwise expressly stated in this specification, an alkyl group is optionally substituted, and the substituents are defined below regarding "optionally substituted". In certain embodiments, the alkyl group has zero branches (i.e., a straight chain), one branch, two branches, or a plurality of branches.

[0020] The term "alkylene" as used herein refers to a divalent group remaining after the above-mentioned alkyl group further loses one hydrogen atom. Unless otherwise specified in the specification, the alkylene group may also be optionally substituted.

[0021] The term "alkyl" as used herein is a straight-chain or branched saturated monovalent hydrocarbon group. Preferably, the alkyl group has 1 to 24 carbon atoms (C1-C 24 alkyl), for example having 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, but are not limited to, 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 10Unless otherwise expressly stated in the specification, an alkyl group may be optionally substituted.

[0022] The term "alkylene" as used herein refers to a divalent group remaining after the above-mentioned alkyl group further loses one hydrogen atom. Unless otherwise specified in the present specification, the alkylene group may also be optionally substituted.

[0023] The term "alkenyl" as used herein is a linear or branched monovalent hydrocarbon group containing one or more double bonds (C=C). Preferably, the alkenyl group has 2 to 24 carbon atoms (C2-C 24 alkenyl), for example, having 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 has 1, 2, 3, 4 or more double bonds. Alkenyl includes but is not limited to C2-C 24 Alkenyl, C2-C 22 Alkenyl, C2-C 20 Alkenyl, C2-C 18 Alkenyl, C2-C 16 Alkenyl, C2-C 12 Alkenyl, C2-C 10 In some embodiments, the alkenyl group has 1 double bond. ...

[0024] The term "alkenylene" used herein refers to a divalent group remaining after the above alkenyl group further loses one hydrogen atom. Unless otherwise specified in the specification, the alkenylene group may also be optionally substituted.

[0025] The term "alkynyl" as used herein is a linear or branched monovalent hydrocarbon radical containing one or more triple bonds (C≡C). Preferably, the alkynyl radical has 2 to 24 carbon atoms (C2-C 24 alkynyl), for example, having 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) and have 1, 2, 3, 4 or more triple bonds. Alkynyl includes but is not limited to C2-C 24 Alkynyl, C2-C 22 Alkynyl, C2-C 20 Alkynyl, C2-C 18 Alkynyl, C2-C 16 Alkynyl, C2-C 12 Alkynyl, C2-C 10 Alkynyl, C2-C8 alkynyl, C2-C7 alkynyl, C2-C6 alkynyl, C2-C4 alkynyl, C2-C3 alkynyl, C4-C8 alkynyl, C4-C9 alkynyl, C5-C8 alkynyl, it has 1,2,3,4 or more triple bonds.Some more specific examples include but are not limited to ethynyl, propynyl, but-1-ynyl, but-2-ynyl, pent-1-ynyl, pent-2-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hept-1-ynyl, hept-2-ynyl, hept-3-ynyl, oct-1-ynyl, oct-2-ynyl, oct-3-ynyl, non-1-ynyl, non-2-ynyl and non-3-ynyl.In some embodiments, the alkynyl has 1 triple bond.Unless otherwise clearly stated in this manual, alkynyl is optionally substituted.

[0026] The term "alkynylene" as used herein refers to a divalent group remaining after the above-mentioned alkynyl group further loses one hydrogen atom. Unless otherwise specified in the specification, an alkynylene group may also be optionally substituted.

[0027] As used herein, the terms "cycloalkyl", "cycloalkylene" and "hydrocarbon ring" refer to saturated (i.e., "cycloalkyl" and "cycloalkylene") or unsaturated (i.e., having one or more double bonds (cycloalkenyl) and / or triple bonds (cycloalkynyl) within the ring) monocyclic or polycyclic hydrocarbon rings having ring carbon atoms. In certain embodiments, "cycloalkyl", "cycloalkylene" and "hydrocarbon ring" have, for example, 3-10, suitably 3-8, more suitably 3-6, such as 5-6 or 5-7, ring carbon atoms. "Cycloalkyl", "cycloalkylene" and "hydrocarbon ring" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclohexenyl and the like. Unless stated otherwise specifically in the specification, cycloalkyl, cycloalkylene and hydrocarbon rings are optionally substituted.

[0028] The term "cycloalkyl" as used herein refers to a saturated monocyclic or polycyclic (such as bicyclic) hydrocarbon ring (e.g., monocyclic, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or bicyclic, including spirocyclic, fused or bridged systems, such as bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl or bicyclo[5.2.0]nonyl, decalinyl, etc.). In certain embodiments, cycloalkyl has, for example, 3 to 10, for example, 3-7, 5-6 or 5-7 carbon atoms. Unless otherwise expressly stated in this specification, cycloalkyl is optionally substituted.

[0029] As used herein, the term "heteroalkyl" or its subordinate concepts (such as heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, etc.) refers to a stable straight-chain, branched or cyclic hydrocarbon radical or a combination thereof, consisting of a certain number of carbon atoms and at least one heteroatom. Heteroatom refers to atoms other than carbon and hydrogen. In certain embodiments, heteroalkyl contains one, two, or more heteroatoms. In certain embodiments, heteroalkyl contains one or more identical or different heteroatoms. Preferably, the heteroatoms are selected from O, N and S. Examples of heteroalkyl 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 specifically in the specification, heteroalkyl groups are optionally substituted.

[0030] As used herein, the term "heteroalkylene" or its subordinate concepts (such as heteroalkylene, heteroalkenylene, heteroalkynylene, heteroarylene, etc.) means a divalent group remaining after the heteroalkyl group as defined above further loses one hydrogen atom. Unless otherwise explicitly stated in this specification, heteroalkylene or its subordinate concepts (such as heteroalkylene, heteroalkenylene, heteroalkynylene, heteroarylene, etc.) are also optionally substituted.

[0031] As used herein, the term "heterocycle", "heterocyclyl" or "heterocyclylene" means a cyclic group having a cyclic structure and containing one or more heteroatoms in the ring-forming atoms. In certain embodiments, the one or more heteroatoms contained in the ring-forming atoms are 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. The "heterocycle", "heterocyclyl" or "heterocyclylene" disclosed herein are saturated or unsaturated. In certain embodiments, the "heterocycle", "heterocyclyl" or "heterocyclylene" comprises a monocycle, a bicycle, or a polycycle. In certain embodiments, the "heterocycle", "heterocyclyl" or "heterocyclylene" is a 4- to 10-membered heterocycle, for example a 4- to 7-membered heterocycle, a 5- to 7-membered heterocycle. Preferably, in certain embodiments, the heterocycle is an optionally substituted 4- to 10-membered heterocycle, wherein the ring-forming atoms contain 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O and S. More preferably, the heterocycle is a 4 to 7 membered saturated heterocycle which may be optionally substituted, wherein the ring-forming atoms include 1, 2, 3 or 4 heteroatoms selected from N, O and S; more preferably, the heterocycle is a 5 to 7 membered (e.g., 5 to 6 membered) saturated heterocycle which may be optionally substituted, wherein the ring-forming atoms include 1, 2 or 3 heteroatoms selected from N, O and S. Examples of heterocycles include, but are not limited to, azetidine, oxetanyl, tetrahydrofuran, pyrrolidine, imidazolidine, pyrazolidine, tetrahydropyran, piperidine, morpholine, thiomorpholine, piperazine, preferably pyrrolidine, piperidine, piperazine and morpholine. The heterocycle may be optionally substituted with one or more substituents, and substituents are defined below for "optionally substituted". Unless otherwise expressly stated in this specification, a heterocycle, heterocyclyl or heterocyclylene group may be optionally substituted.

[0032] As used herein, the term "aryl" refers to an all-carbon monocyclic or fused-ring polycyclic aromatic group having a conjugated π electron system. For example, as used herein, the term "C 6-14 "Aryl" means an aromatic group containing 6 to 14 (eg 6 to 12) carbon atoms, such as phenyl or naphthyl. Unless stated otherwise specifically in the specification, an aryl group is optionally substituted.

[0033] As used herein, the term "heteroaryl" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic) aromatic group having a conjugated π electron system, the ring atoms of which are composed of carbon atoms and at least one heteroatom, for example, having 5 to 14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms, wherein there are 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). One or more of the ring carbon atoms in the heteroaryl group may be replaced by C(O). The heteroaryl group may be benzo-fused. Unless otherwise expressly stated in this specification, the heteroaryl group is optionally substituted.

[0034] 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. The substituents are independently selected from, but not limited to, deuterium (D), tritium (T), halogen, -OH, mercapto, cyano, -CD3, C1-C6 alkyl (preferably C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl (preferably C3-C8 cycloalkyl), aryl, heterocyclyl (preferably 3-8 membered heterocyclyl), heteroaryl, aryl C1-C6 alkyl, heteroaryl C1-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-SH, C1-C6 alkyl-O-C1-C6 alkyl, OC1-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 C1-C6 alkyl), -CONRiRii (wherein Ri and / or Rii is 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)-5-7 membered heteroaryl), -C(O)C1-C6 alkylphenyl, -C(O)C1-C6 haloalkyl, -OC(O)C1-C6 alkyl (preferably -OC(O) )C1-C3 alkyl), -S(O)2-C1-C6 alkyl, -S(O)-C1-C6 alkyl, -S(O)2-phenyl, -S(O)2-C1-C6 haloalkyl, -S(O)2NH2, -S(O)2NH(C1-C6 alkyl), -S(O)2NH(phenyl), -NHS(O)2(C1-C6 alkyl), -NHS(O)2(phenyl) and -NHS(O)2(C1-C6 haloalkyl), wherein each of said alkyl, cycloalkyl, phenyl, aryl, heterocyclyl and heteroaryl is optionally further substituted with one or more substituents selected from the following:But not limited to: halogen, -OH, -NH2, cycloalkyl, 3-8 membered heterocyclyl, C1-C4 alkyl, C1-C4 haloalkyl-, -OC1-C4 alkyl, -C1-C4 alkyl-OH, -C1-C4 alkyl-O-C1-C4 alkyl, -OC1-C4 haloalkyl, cyano, nitro, -C(O)-OH, -C(O)OC1-C6 alkyl, -CON(C1-C6 alkyl)2, -CONH(C1-C6 alkyl), -CON H2, -NHC(O)(C1-C6 alkyl), -NH(C1-C6 alkyl)C(O)(C1-C6 alkyl), -SO2(C1-C6 alkyl), -SO2(phenyl), -SO2(C1-C6 haloalkyl), -SO2NH2, -SO2NH(C1-C6 alkyl), -SO2NH(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. ,

[0035] In certain embodiments, the substituents can be independently selected from, but are not limited to, halogen (e.g., chlorine, bromine, fluorine, or iodine), carboxylic acid (e.g., -C(=O)OH), oxygen (e.g., =O), sulfur (e.g., =S), hydroxyl (e.g., -OH), ester (e.g., -C(=O)ORiii or -OC(=O)Riii), aldehyde (e.g., -C(=O)H), carbonyl (e.g., -C(=O)Riii, or represented by C=O), acyl halide (e.g., -C(=O)X, wherein X is selected from bromine, fluorine, chlorine, or iodine), carbonate (e.g., -OC(=O)ORiii), alkoxy (e.g., -ORiii), acetal (e.g., -C(ORiii)2Riii, wherein each ORiii is the same or different alkoxy), phosphate (e.g., P(=O)4 3- ), sulfhydryl (e.g. -SH), sulfoxide (e.g. -S(=O)Riii), sulfinic acid (e.g. -S(=O)OH), sulfonic acid (e.g. -S(=O)2OH), thialdehyde (e.g. -C(=S)H), sulfate (e.g. S(=O)4 2-), sulfonyl (e.g., -S(=O)2Riii), sulfinyl (e.g., -S(=O)Riii), amide (e.g., -C(=O)N(Riii)2 or -N(Riii)C(=O)Riii), azido (e.g., -N3), nitro (e.g., -NO2), cyano (e.g., -CN), isocyano (e.g., -NC), acyloxy (e.g., -OC(=O)Riii), amino (e.g., -N(Riii)2, -N(Riii)H or -NH2), carbamoyl (e.g., -OC(=O)N(Riii)2, -OC(=O)N(Riii) i) H or -OC(=O)NH2), sulfonamide (e.g., -S(=O)2N(Riii)2, -S(=O)2N(Riii)H, -S(=O)2NH2, -N(Riii)S(=O)2Riii, -N(H)S(=O)2Riii, -N(Riii)S(=O)2H or -N(H)S(=O)2H), alkyl, alkenyl, alkynyl, cycloalkyl (e.g., cycloalkyl, cycloalkenyl or cycloalkynyl), heterocycloalkyl (e.g., heterocycloalkyl containing one or more heteroatoms selected from S, N and O, or containing one or more heteroatoms selected from S, N and O heterocycloalkenyl), aryl (e.g., phenyl, or fused ring), heteroaryl (e.g., 8- to 10-membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur), -C(=O)SRiii, -C(=N-CN)N(Riii)2, -C(=NO-CH3)N(Riii)2, -C(=N-SO2-NH2)N(Riii)2, -C(=CH-NO2)N(Riii)2, -OC(=O)N(Riii)2, -CHN(Riii)N(Riii)2, -C(=O)N(Riii)ORiii, - N(Riii)2C(=O)ORiii、-OP(=O)(ORiii)2、-P(=O)(ORiii)2、-N(ORiii)C(=O)Riii、-N(ORiii)S(=O)2Riii、-N(ORiii)C(=O)ORiii、-N(ORiii)C(=O)N(Riii)2、-N(ORiii)C(=S)N(Riii)2、-N(ORiii)C(NRiii)N(Riii)2、-N(ORiii)C(CHRiii)N(Riii)2。In any of the foregoing, Riii is hydrogen as defined herein, or alkyl, or alkenyl, or alkynyl, or heteroalkyl, or heteroalkenyl, or heteroalkynyl. In some embodiments, Riii is hydrogen as defined herein, or C1-C 12 Alkyl, or C2-C 12 Alkenyl, or C2-C 12 Alkynyl, or C2-C 12 Heteroalkyl, or C3-C12 Heteroalkenyl, or C3-C 12 Heteroalkynyl.

[0036] In certain embodiments, the substituent itself can be further substituted by, for example, one or more substituents as defined herein. For example, a C1-C6 alkyl group as a substituent can be further substituted by one or more substituents as described herein.

[0037] As used herein, the term "halo" or "halogen" group is defined to include F, Cl, Br, or I.

[0038] As used herein, "pharmaceutically acceptable salts" refer to acid addition salts or base addition salts of the disclosed compounds that retain the biological effectiveness and properties of the disclosed compounds and, generally, are not 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.

[0039] Pharmaceutically acceptable acid addition salts can be formed with inorganic and / or organic acids such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, decanoic 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, galactose disulfonic acid, 1,2-di ... Acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphate, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid and undecylenic acid, etc.

[0040] Pharmaceutically acceptable base addition salts can be formed with inorganic bases and / or organic bases and the compounds of the present disclosure. 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, etc. 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, secondary, tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, denanol, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benethamine, benzathine, ethylenediamine, glucosamine, methylglucamine, theobromine, triethanolamine, tromethamine, purine, piperazine, piperidine, N-ethylpiperidine, and polyamine resins. Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0041] The numerical ranges described herein should be understood to encompass the boundary values ​​and any and all subranges contained therein. For example, the range "1 to 10" should be understood to include not only the explicitly stated values ​​of 1 and 10, but also any individual value (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 that use only one value as the minimum or maximum value.

[0042] As used herein, the term "isomer" means different compounds with the same molecular formula. "Stereoisomers" are isomers that differ only in the way their atoms are arranged 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 referred to as a "racemic" mixture. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. "Tautomers" refer to isomeric forms of a compound that are in equilibrium with each other. The concentrations of the isomeric forms will depend on the environment in which the compound is found and may vary depending on, for example, whether the compound is a solid or in an organic or aqueous solution.

[0043] In certain embodiments, "stereoisomers" may also include E and Z isomers or mixtures thereof, as well as cis and trans isomers or mixtures thereof.

[0044] The nucleic acids and / or polynucleotides useful in the present disclosure include a coding region encoding a polypeptide of interest, a 5′-UTR located at the 5′-end of the coding region, and a 3′-UTR located at the 3′-end of the coding region. In some embodiments, the nucleic acid or polynucleotide further includes at least one of a polyadenylation region and a Kozak sequence. In some embodiments, the nucleic acid or polynucleotide (e.g., mRNA) may further include a 5′ cap structure. Any region of the nucleic acid may include one or more alternative nucleosides, such as 5-substituted uridines (e.g., 5-methoxyuridine), 1-substituted pseudouridines (e.g., 1-methyl-pseudouridine or 1-ethyl-pseudouridine), and / or 5-substituted cytidines (e.g., 5-methyl-cytidine).

[0045] The term "5'-UTR" or "5' untranslated region" can refer to an RNA sequence in an mRNA that is upstream of a coding sequence and is not translated into protein. The 5'-UTR in a gene typically begins at the transcription start site and ends at the nucleotides upstream of the translation start codon of the coding sequence. The 5'-UTR can contain elements that control gene expression, such as a ribosome binding site, a 5'-terminal oligopyrimidine tract, and a translation initiation signal such as a Kozak sequence. mRNA can be post-transcriptionally modified by the addition of a 5' cap. Therefore, the 5'-UTR in a mature mRNA can also refer to the RNA sequence between the 5' cap and the start codon. As used herein, the term "3' untranslated region" or "3'-UTR" can refer to an RNA sequence that is downstream of a coding sequence and is not translated into protein. The 3'-UTR in an mRNA is located between the stop codon and the poly(A) sequence of the coding sequence, for example, starting at the nucleotides downstream of the stop codon and ending at the nucleotides upstream of the poly(A) sequence. The sequence of the 5′-UTR and / or 3′-UTR may be homologous or heterologous to the sequence of the coding region. The 3′-UTR may comprise a 3′-UTR derived from at least one of an albumin gene, an α-globin gene, a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene, and a collagen α gene.

[0046] As used herein, the term "poly(A) region" is used interchangeably with "poly(A) sequence" and "poly(A) tail", and naturally occurring poly(A) sequences are typically composed of adenine ribonucleotides. Preferably, a "poly(A) region" refers to a poly(A) sequence comprising nucleotides or nucleotide segments other than adenine ribonucleotides. The poly(A) sequence is typically located at the 3' end of the mRNA, such as the 3' end (downstream) of the 3'-UTR. The poly-A region may have different lengths. Specifically, in some embodiments, the poly-A region of the nucleic acid molecules of the present disclosure has a length of at least 30 nucleotides; in some embodiments, the poly-A region of the nucleic acid molecules of the present disclosure has a length of at least 80 nucleotides; in some embodiments, the poly-A region of the nucleic acid molecules of the present disclosure has a length of at least 100 nucleotides.

[0047] As used herein, the term "5' cap structure": The 5' cap structure is generally located at the 5' end of the mature mRNA. In some embodiments, the 5' cap structure is linked to the 5' end of the mRNA via a 5'-5'-triphosphate bond. The 5' cap structure is generally formed by modified (e.g., methylated) ribonucleotides (especially guanine nucleotide derivatives). For example, m7GpppN (cap 0 or "cap0" is a cap structure formed by the 5' phosphate group of the hnRNA reacting with the 5'-phosphate group of the m7GTP under the action of guanylyl transferase to form a 5', 5'-phosphodiester bond), wherein N is the terminal 5' nucleotide of the nucleic acid carrying the 5' cap structure. In some embodiments, the 5′ cap structure includes, but is not limited to, cap 0, cap 1 (a cap structure formed by further methylating the 2′-OH of the first nucleotide sugar group of hnRNA on the basis of cap 0, or referred to as “cap 1”), cap 2 (a cap structure formed by further methylating the 2′-OH of the second nucleotide sugar group of hnRNA on the basis of cap 1, or referred to as “cap 2”), cap 4, cap 0 analogs, cap 1 analogs, cap 2 analogs, or cap 4 analogs.

[0048] Amino lipid compounds

[0049] In one aspect, the present disclosure provides an amino lipid compound represented by the following formula (I):

[0050] or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

[0051] in,

[0052] A1, A2, and A3 are one of the following:

[0053] (1) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is a C1-C5 alkyl group or a C1-C5 heteroalkyl group, A2 is a C1-C5 alkyl group or a C1-C5 heteroalkyl group, and A3 is a C1-C5 alkylene group or a bond;

[0054] (2) when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C3 alkylene or C1-C3 heteroalkylene, A2 is C1-C3 alkylene or C1-C3 heteroalkylene, A3 is C1-C5 alkylene or a bond, and A1 and A2 together with the nitrogen atom to which they are commonly attached form a four-membered ring, a five-membered ring, or a six-membered ring; or

[0055] (3) When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C3 alkylene or C1-C3 heteroalkylene, A2 is C1-C5 alkyl or C1-C5 heteroalkyl, A3 is C1-C5 alkylene, and A1 and A3, together with the nitrogen atom to which they are commonly attached, form a four-membered ring, a five-membered ring, or a six-membered ring;

[0056] A4 is a C1-C5 alkylene group or a bond;

[0057] A5 is C1-C 16 alkylene group or bond;

[0058] A6 is C1-C 16 alkylene group or bond;

[0059] A7 is C1-C 18 alkylene group or bond;

[0060] A8 is C1-C 18 alkylene group or bond;

[0061] Z1 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)NR3- or -NR3C(=O)-;

[0062] R3 is H or C1-C8 alkylene;

[0063] Z2 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)NR4- or -NR4C(=O)-;

[0064] R4 is H or C1-C3 alkylene;

[0065] Y is -Z3C(=O)Z4-, -N(R5)-;

[0066] Z3 is -O-, -N(R6)-, -S- or a bond;

[0067] Z4 is -O-, -N(R7)-, -S- or a bond;

[0068] R5 is -C(=O)A9Z5A 10 or -C(=O)A 11 ;

[0069] Z5 is -O- or ‐S‐;

[0070] A9 is a C1-C3 alkylene group or a bond;

[0071] A 10 is a C1-C8 hydrocarbon group;

[0072] A 11 is a C1-C3 hydrocarbon group;

[0073] R6 is H, C1-C8 hydrocarbon group;

[0074] R7 is H, C1-C8 hydrocarbon group;

[0075] X is C or N;

[0076] R1 is H or C1-C 18 alkyl, Z6R8 or -CH(OR9)2;

[0077] Z6 is -C(=O)O-, -OC(=O)-, or -O-;

[0078] R8 is H, C1-C 18 Hydrocarbon, C1-C containing O or S 18 heteroalkyl;

[0079] R9 is C1-C 18 Hydrocarbon, C1-C containing O or S 18 heteroalkyl;

[0080] R2 is H or C1-C 18 Hydrocarbon, Z7R 10 or-CH(OR 11 )2;

[0081] Z7 is -C(=O)O-, -OC(=O)-, or -O-;

[0082] R 10 H, C1-C 18 Hydrocarbon, C1-C containing O or S 18 heteroalkyl;

[0083] R 11 C1-C 18Hydrocarbon, C1-C containing O or S 18 heteroalkyl;

[0084] Preferably, the hydrocarbon group is an alkyl group, an alkenyl group or an alkynyl group;

[0085] Preferably, the hydrocarbylene group is an alkylene group, an alkenylene group or an alkynylene group;

[0086] Preferably, the heteroalkyl group is a heteroalkyl group, a heteroalkenyl group or a heteroalkynyl group.

[0087] In some embodiments, the present disclosure provides an amino lipid compound of formula (I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R1 is Z6R8 or -CH(OR9)2, R2 is Z7R 10 or-CH(OR 11 )2.

[0088] In some embodiments, in the amino lipid compound represented by formula (I), when the dotted line connecting A1 and A2 and the dotted line connecting A1 and A3 are absent, A1 is a C1-C5 alkyl or C1-C5 heteroalkyl, A2 is a C1-C5 alkyl or C1-C5 heteroalkyl, and A3 is a C1-C5 alkylene group or a bond, that is, it has the structure shown in formula (Ia):

[0089] wherein A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1 and R2 are as defined in formula (I).

[0090] In some embodiments, in the amino lipid compound represented by formula (I), when the dotted line connecting A1 and A2 is a bond and the dotted line connecting A1 and A3 is absent, A1 is a C1-C3 alkylene group or a C1-C3 heteroalkylene group, A2 is a C1-C3 alkylene group or a C1-C3 heteroalkylene group, A3 is a C1-C5 alkylene group or a bond, and A1 and A2 together with the nitrogen atom to which they are commonly connected form a four-membered ring, a five-membered ring or a six-membered ring, i.e., having a structure shown in formula (Ib):

[0091] wherein A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1 and R2 are as defined in formula (I).

[0092] In some embodiments, in the amino lipid compound represented by formula (I), when the dotted line connecting A1 and A3 is a bond and the dotted line connecting A1 and A2 is absent, A1 is a C1-C3 alkylene group or a C1-C3 heteroalkylene group, A2 is a C1-C5 alkyl group or a C1-C5 heteroalkyl group, A3 is a C1-C5 alkylene group, and A1 and A3 together with the nitrogen atom to which they are commonly connected form a four-membered ring, a five-membered ring, or a six-membered ring, i.e., having the structure shown in formula (Ic):

[0093] wherein A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1 and R2 are as defined in formula (I).

[0094] In some embodiments, in the amino lipid compound represented by formula (I), when X is C, it has a structure represented by formula (Id):

[0095] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R1 and R2 are as defined in formula (I).

[0096] In some embodiments, in the amino lipid compound represented by formula (I), when X is N, it has a structure represented by formula (Ie):

[0097] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R1 and R2 are as defined in formula (I).

[0098] In some embodiments, in the amino lipid compound represented by formula (I), when R1 is -CH(OR9)2, it has a structure represented by formula (II):

[0099] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, X, R2 and R9 are as defined in formula (I).

[0100] In some embodiments, in the amino lipid compound represented by formula (II), when X is C, it has a structure represented by formula (IIa):

[0101] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R2 and R9 are as defined in formula (I).

[0102] In some embodiments, in the amino lipid compound represented by formula (II), when X is N, it has a structure represented by formula (IIb):

[0103] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R2 and R9 are as defined in formula (I).

[0104] In some embodiments, in the amino lipid compound represented by formula (I), when

[0105] R1 is -CH(OR9)2;

[0106] R2 is -CH(OR 11 )2 o'clock,

[0107] That is, it has the structure shown in formula (III):

[0108] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, X, R9 and R 11 The definition of is as defined in formula (I).

[0109] In some embodiments, in the amino lipid compound represented by formula (III), when X is C, it has a structure represented by formula (IIIa):

[0110] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R9 and R 11 The definition of is as defined in formula (I).

[0111] In some embodiments, in the amino lipid compound represented by formula (III), when X is N, it has a structure represented by formula (IIIb):

[0112] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R9 and R 11 The definition of is as defined in formula (I).

[0113] In some embodiments, in the amino lipid compound represented by formula (I), when

[0114] Y is -Z3C(=O)Z4-;

[0115] Z3 is -O-;

[0116] Z4 is -O-;

[0117] X is C;

[0118] R1 is -CH(OR9)2 and R2 is -CH(OR 11 )2 o'clock,

[0119] That is, it has the structure shown in formula (IV):

[0120] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9 and R 11 The definition of is as defined in formula (I).

[0121] In some embodiments, in the amino lipid compound represented by formula (I), when

[0122] Y is -Z3C(=O)Z4-;

[0123] Z3 is -O-;

[0124] Z4 is -O-;

[0125] X is C;

[0126] Z1 is ‐C(=O)O‐, ‐OC(=O)‐;

[0127] Z2 is ‐C(=O)O‐, ‐OC(=O)‐;

[0128] R1 is -CH(OR9)2 and R2 is -CH(OR 11 )2 o'clock,

[0129] That is, it has the structure shown in formula (Va), (Vb), (Vc) or (Vd):

[0130] Among them, A1, A2, A3, A4, A5, A6, A7, A8, R9 and R 11 The definition of is as defined in formula (I).

[0131] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0132] A1 is C1, C2, C3, C4, C5 hydrocarbon group, C1, C2, C3, C4, C5 heterohydrocarbon group, C1, C2, C3 hydrocarbon alkylene group, or C1, C2, C3 heterohydrocarbon alkylene group.

[0133] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0134] A2 is C1, C2, C3, C4, C5 hydrocarbon group, C1, C2, C3, C4, C5 heterohydrocarbon group, C1, C2, C3 hydrocarbon alkylene group, or C1, C2, C3 heterohydrocarbon alkylene group.

[0135] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0136] A3 is a C1, C2, C3, C4, or C5 alkylene group or a bond.

[0137] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0138] A4 is a C1, C2, or C3 alkylene group or a bond.

[0139] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0140] A5 is C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 Hydrocarbylene.

[0141] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0142] A6 is C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C11 、C 12 、C 13 、C 14 、C 15 、C 16 Hydrocarbylene.

[0143] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0144] A7 is 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 Hydrocarbylene.

[0145] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0146] A8 is 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 Hydrocarbylene.

[0147] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0148] A9 is a C1, C2, or C3 alkylene group.

[0149] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0150] A 10 It is C1, C2, C3, C4, C5, C6, C7, or C8 alkylene.

[0151] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0152] A 11 It is a C1, C2, or C3 alkylene group.

[0153] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0154] R6 is H or C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbon group.

[0155] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0156] R7 is H or C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbon group.

[0157] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), or (IV) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0158] R3 is H or C1, C2, C3, C4, C5, C6, C7, or C8 alkylene.

[0159] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), or (IV) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0160] R4 is H or C1, C2, or C3 alkylene.

[0161] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), or (IV) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0162] R4 is an optionally substituted C1-C3 alkylene group;

[0163] Preferably, R4 is a C1-C3 alkylene group optionally substituted by a hydroxyl group, an ester group, an alkoxy group, an alkyl group, a halogen, an oxygen group, a sulfur group, an amino group, or an amide group.

[0164] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib) (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0165] R1 is H or C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Hydrocarbon group.

[0166] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib) (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0167] R1 is H, C1-C 18 Straight chain alkyl, C2-C 18 Straight chain alkenyl, or C2-C 18 A straight-chain alkynyl group.

[0168] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib) (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0169] R1 is 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 Straight chain alkyl, or 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 Straight chain alkenyl, or 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 A straight-chain alkynyl group.

[0170] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib) (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0171] R1 is H, C3-C 18 branched alkyl, C3-C 18 branched alkenyl, or C4-C 18 branched alkynyl.

[0172] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib) (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0173] R1 is C3, C4, C5, C6, C7, C8, C9, C10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Branched alkyl, or 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 Branched alkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 branched alkynyl.

[0174] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0175] R8 is 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 Hydrocarbon, 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 Heteroalkyl.

[0176] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0177] R8 is C1-C 18 Straight chain alkyl, or C2-C 18 Straight chain alkenyl, or C2-C 18 Straight chain alkynyl, or C1-C 18 Straight chain heteroalkyl, or C2-C 18 or a straight-chain heteroalkynyl containing O or S.

[0178] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0179] R8 is 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 Straight chain alkyl, or 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 Straight chain alkenyl, or 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 A straight-chain alkynyl, or a C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C15 、C 16 、C 17 、C 18 Straight chain heteroalkyl, or 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 A straight chain heteroalkenyl, or a 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 A straight-chain heteroalkynyl group.

[0180] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0181] R8 is C3-C 18 branched alkyl, or C3-C 18 branched alkenyl, or C4-C 18 Branched alkynyl, or C3-C containing O or S 18 branched heteroalkyl, or C3-C 18 branched heteroalkenyl, or C4-C 18 Branched chain heteroalkynyl.

[0182] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0183] R8 is C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18Branched alkyl, or 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 Branched alkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 branched alkynyl, or 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 branched heteroalkyl, or 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 branched heteroalkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Branched chain heteroalkynyl.

[0184] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id) or (Ie) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0185] R8 is

[0186] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0187] R9 is 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 Hydrocarbon, 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 Heteroalkyl.

[0188] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0189] R9 is C1-C 18 Straight chain alkyl, or C2-C 18 Straight chain alkenyl, or C2-C 18 Straight chain alkynyl, or C1-C 18 Straight chain heteroalkyl, or C2-C 18 A straight-chain heteroalkenyl group, or a C2-C 18 A straight-chain heteroalkynyl group.

[0190] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0191] R9 is 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 Straight chain alkyl, or 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 Straight chain alkenyl, or 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 A straight-chain alkynyl, or a 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 Straight chain heteroalkyl, or C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C18 A straight chain heteroalkenyl, or a 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 A straight-chain heteroalkynyl group.

[0192] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0193] R9 is C3-C 18 branched alkyl, or C3-C 18 branched alkenyl, or C4-C 18 Branched alkynyl, or C3-C containing O or S 18 branched heteroalkyl, or C3-C 18 branched heteroalkenyl, or C4-C 18 Branched chain heteroalkynyl.

[0194] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0195] R9 is 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 Branched alkyl, or C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C14 、C 15 、C 16 、C 17 、C 18 Branched alkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 branched alkynyl, or 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 branched heteroalkyl, or 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 branched heteroalkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Branched chain heteroalkynyl.

[0196] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0197] R9 is

[0198] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0199] R2 is H or C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Hydrocarbon group.

[0200] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0201] R2 is H, C1-C 18 Straight chain alkyl, C2-C 18 Straight chain alkenyl, or C2-C 18 A straight-chain alkynyl group.

[0202] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0203] R2 is 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 Straight chain alkyl, or 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 18Straight chain alkenyl, or 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 A straight-chain alkynyl group.

[0204] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0205] R2 is H, C3-C 18 branched alkyl, C3-C 18 branched alkenyl, or C4-C 18 branched alkynyl.

[0206] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0207] R2 is 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 Branched alkyl, or 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 Branched alkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C17 、C 18 branched alkynyl.

[0208] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0209] R 10 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 Hydrocarbon, 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 Heteroalkyl.

[0210] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0211] R 10 C1-C 18 Straight chain alkyl, or C2-C 18 Straight chain alkenyl, or C2-C 18 Straight chain alkynyl, or C1-C 18 Straight chain heteroalkyl, or C2-C 18 A straight-chain heteroalkenyl group, or a C2-C 18 A straight-chain heteroalkynyl group.

[0212] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0213] R 10 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 Straight chain alkyl, or 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 Straight chain alkenyl, or 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 A straight-chain alkynyl, or a 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 Straight chain heteroalkyl, or 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 A straight chain heteroalkenyl, or a C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C16 、C 17 、C 18 A straight-chain heteroalkynyl group.

[0214] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0215] R 10 C3-C 18 branched alkyl, or C3-C 18 branched alkenyl, or C4-C 18 Branched alkynyl, or C3-C containing O or S 18 branched heteroalkyl, or C3-C 18 branched heteroalkenyl, or C4-C 18 Branched chain heteroalkynyl.

[0216] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0217] R 10 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 Branched alkyl, or 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 Branched alkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C17 、C 18 branched alkynyl, or 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 branched heteroalkyl, or 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 branched heteroalkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Branched chain heteroalkynyl.

[0218] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (IIb) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0219] R 10 for

[0220] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0221] R 11 C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C13 、C 14 、C 15 、C 16 、C 17 、C 18 Hydrocarbon, 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 Heteroalkyl.

[0222] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0223] R 11 C1-C 18 Straight chain alkyl, or C2-C 18 Straight chain alkenyl, or C2-C 18 Straight chain alkynyl, or C1-C 18 Straight chain heteroalkyl, or C2-C 18 A straight-chain heteroalkenyl group, or a C2-C 18 A straight-chain heteroalkynyl group.

[0224] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0225] R 11 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 、C18 Straight chain alkyl, or 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 Straight chain alkenyl, or 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 A straight-chain alkynyl, or a 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 Straight chain heteroalkyl, or 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 A straight chain heteroalkenyl, or a 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 A straight-chain heteroalkynyl group.

[0226] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0227] R 11 C3-C 18 branched alkyl, or C3-C 18 branched alkenyl, or C4-C 18 Branched alkynyl, or C3-C containing O or S 18 branched heteroalkyl, or C3-C 18 branched heteroalkenyl, or C4-C 18 Branched chain heteroalkynyl.

[0228] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0229] R 11 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 Branched alkyl, or 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 Branched alkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C16 、C 17 、C 18 branched alkynyl, or 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 branched heteroalkyl, or 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 branched heteroalkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Branched chain heteroalkynyl.

[0230] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0231] R 11 for

[0232] In some embodiments, the present disclosure provides an amino lipid compound of Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0233] The hydrocarbyl, hydrocarbylene, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene and heterohydrocarbyl groups are optionally substituted;

[0234] Optionally, the hydrocarbyl, hydrocarbylene, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene and heterohydrocarbyl groups are optionally substituted with hydroxy, ester, hydrocarbyloxy, hydrocarbyl, halogen, oxygen, sulfur, amino, amide groups.

[0235] In another aspect, the present disclosure provides an amino lipid compound represented by the following formula (II-I):

[0236] or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

[0237] in,

[0238] A1, A2, and A3 are one of the following:

[0239] (1) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, and A3 is C1-C5 alkylene or a bond;

[0240] (2) when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene or a bond, and A1 and A2 together with the nitrogen atom to which they are attached form a nitrogen-containing heterocyclic ring; or

[0241] (3) When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A3 is C1-C5 alkylene, and A1 and A3, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocycle;

[0242] (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene, and A1, A2 and A3, together with the nitrogen atom to which they are commonly attached, form a spirocyclic heterocycle, a fused heterocycle or a bridged heterocycle containing N;

[0243] A4 is a C1-C5 alkylene group or a bond;

[0244] A5, A6, A7, A8 and A 12 Each independently C1-C 18alkylene group or bond;

[0245] Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0246] Y1 is -Z3C(=O)Z4-, -N(R5)-, -Z3C(=S)Z4-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP (=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -O-, -S-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S- or -SC(=O)O-;

[0247] X is C or N;

[0248] R1 is H, C1-C 24 Hydrocarbon, C1-C 24 heteroalkyl, Z6R8 or -CH(OR9)2;

[0249] R2 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z7R 10 or-CH(OR 11 )2;

[0250] Z3 and Z4 are each independently -O-, -N(R6)-, -S- or a bond;

[0251] Z6 and Z7 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0252] R5 is -C(=O)A9Z5A 10 、-C(=O)A 11 , H or C1-C8 hydrocarbon group;

[0253] Z5 is -O- or ‐S‐;

[0254] R6 are each independently H or C1-C8 hydrocarbon group;

[0255] R8 and R 10 Each independently represents H, C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0256] R9 and R 11 Each independently C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0257] A9 is a C1-C8 alkylene group or a bond;

[0258] A 10 and A 11 Each is independently a C1-C8 hydrocarbon group;

[0259] Preferably, the hydrocarbon group is an alkyl group, an alkenyl group or an alkynyl group;

[0260] Preferably, the hydrocarbylene group is an alkylene group, an alkenylene group or an alkynylene group;

[0261] Preferably, the heteroalkyl group is a heteroalkyl group, a heteroalkenyl group or a heteroalkynyl group;

[0262] Preferably, the heteroalkylene group is a heteroalkylene group, a heteroalkenylene group or a heteroalkynylene group.

[0263] In yet another aspect, the present disclosure provides an amino lipid compound represented by the following formula (II-I):

[0264] or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

[0265] in,

[0266] A1, A2, and A3 are one of the following:

[0267] (1) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, and A3 is C1-C5 alkylene or a bond;

[0268] (2) When the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene or a bond, and A1 and A2, together with the nitrogen atom to which they are commonly attached, form a nitrogen-containing heterocyclic ring;

[0269] (3) When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A3 is C1-C5 alkylene, and A1 and A3, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocycle;

[0270] (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene, and A1, A2 and A3, together with the nitrogen atom to which they are commonly attached, form a spirocyclic heterocycle, a fused heterocycle or a bridged heterocycle containing N;

[0271] A4 is a C1-C5 alkylene group or a bond;

[0272] A5, A6, A7, A8 and A 12 Each independently C1-C18 Alkylidene, C1-C 18 heteroalkylene or bond;

[0273] Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0274] Y1 is -Z3C(=O)Z4-, -N(R5)-, -Z3C(=S)Z4-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP (=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -O-, -S-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S- or -SC(=O)O-;

[0275] X is C or N;

[0276] R1 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z6R8, -C(R6)(OA 13 Z8R9)2、-C(R6)(SA 13 Z8R9)2 or -C(R6)(SA 13 Z8R9)(OA 13 Z8R9);

[0277] R2 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z7R 10 、-C(R6)(OA 14 Z9R 11 )2、-C(R6)(SA 14 Z9R 11 )2 or -C(R6)(SA 14 Z9R 11 )(OA 14 Z9R 11 );

[0278] Z3 and Z4 are each independently -O-, -N(R6)-, -S- or a bond;

[0279] Z6 and Z7 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0280] R5 is -C(=O)A9Z5A 10 、-C(=O)A 11 , H or C1-C8 hydrocarbon group;

[0281] Z5 is -O- or ‐S‐;

[0282] Z8 and Z9 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S -, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(=O)2O- or bond;

[0283] R6 are each independently H or C1-C8 hydrocarbon group;

[0284] R8 and R 10 Each independently represents H, C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0285] R9 and R 11 Each independently C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0286] A9 is a C1-C8 alkylene group or a bond;

[0287] A 10 and A 11 Each is independently a C1-C8 hydrocarbon group;

[0288] A 13 and A 14 are each independently C1-C8 alkylene, C1-C8 heteroalkylene or a bond;

[0289] Preferably, the hydrocarbon group is an alkyl group, an alkenyl group or an alkynyl group;

[0290] Preferably, the hydrocarbylene group is an alkylene group, an alkenylene group or an alkynylene group;

[0291] Preferably, the heteroalkyl group is a heteroalkyl group, a heteroalkenyl group or a heteroalkynyl group;

[0292] Preferably, the heteroalkylene group is a heteroalkylene group, a heteroalkenylene group or a heteroalkynylene group.

[0293] The present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, when applicable, including one or more of the following features.

[0294] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0295] A1 is H, A2 is H; or A1 is H, A2 is not H; or A1 is not H, A2 is H.

[0296] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0297] A1 and A2 are each independently a C1, C2, C3, C4, C5 hydrocarbon group, or a C1, C2, C3, C4, C5 heterohydrocarbon group, or a C1, C2, C3, C4, C5 alkylene group, or a C1, C2, C3, C4, C5 heterohydrocarbonene group.

[0298] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0299] A1 and A2 are each independently C1-C5 alkyl, or C2-C5 alkenyl having 1 or 2 double bonds, or C2-C5 alkynyl having 1 or 2 triple bonds, or C1-C5 heteroalkyl containing S or O, or C2-C5 heteroalkenyl containing S or O having 1 or 2 double bonds, or C2-C5 heteroalkynyl containing S or O having 1 or 2 triple bonds, or C1-C5 alkylene, or C2-C5 alkenylene having 1 or 2 double bonds, or C2-C5 alkynylene having 1 or 2 triple bonds, or C1-C5 heteroalkylene containing S or O, or C2-C5 heteroalkenylene containing S or O having 1 or 2 double bonds, or C2-C5 heteroalkynylene containing S or O.

[0300] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0301] A1 and / or A2 is an unsubstituted C1-C5 hydrocarbon group, or an unsubstituted C1-C5 heterohydrocarbon group, or an unsubstituted C1-C5 alkylene group, or an unsubstituted C1-C5 heteroalkylene group.

[0302] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0303] A1 and / or A2 is a substituted C1-C5 hydrocarbon group, or a substituted C1-C5 heterohydrocarbon group, or a substituted C1-C5 alkylene group, or a substituted C1-C5 heteroalkylene group.

[0304] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0305] A1 and / or A2 is a substituted C1-C5 alkyl, or a substituted C2-C5 alkenyl, or a substituted C3-C5 alkynyl, or a substituted C1-C5 alkylene, or a substituted C2-C5 alkenylene, or a substituted C3-C5 alkynylene.

[0306] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0307] A1 and / or A2 is hydroxy, cyano, phenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5- to 6-membered monocyclic group, heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 8- to 10-membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, -OR 12 ,-C(=O)R 12 ,-C(=O)SR 12 ,-OC(=O)R 12 ,-OC(=O)OR 12 ,-N(R 12 )2,-C(=O)N(R 12 )2,-C(=S)N(R 12 )2,-S(=O)2R 12 ,-S(=O)2N(R 12 )2,-OC(=O)N(R 12 )2,-CH(NR 12 )N(R 12 )2,-C(NR 12 )2R 12,-C(=O)N(R 12 )OR 12 ,-CH(R 12 )N(R 12 )2C(=O)OR 12 ,-C(R 12 )3,-N(R 12 )C(=O)R 12 ,-N(R 12 )C(=O)OR 12 ,-N(R 12 )S(=O)2R 12 ,-N(R 12 )C(=O)N(R 12 )2,-N(R 12 )C(=S)N(R 12 )2,-N(R 12 )C(NR 12 )N(R 12 )2,-N(R 12 )C(CHR 12 )N(R 12 )2,-N(OR 12 )C(=O)R 12 ,-N(OR 12 )S(=O)2R 12 ,-N(OR 12 )C(=O)OR 12 ,-N(OR 12 )C(=O)N(R 12 )2,-N(OR 12 )C(=S)N(R 12 )2,-N(OR 12 )C(NR 12 )N(R 12 )2,-N(OR 12 )C(CHR 12 )N(R 12 )2,-OP(=O)(OR 12 )2,-P(=O)(OR 12 )2, or a 3- to 7-membered alicyclic and 3- to 7-membered heterocyclic ring containing 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2,-C(=NO-CH3)N(R 12 )2,-C(=N-SO2-NH2)N(R 12 )2,-C(=CH-NO2)N(R 12 )2 or -C(=O)OR 12Substituted C1-C5 alkyl, C2-C5 alkenyl, C3-C5 alkynyl, C1-C5 alkylene, C2-C5 alkenylene, C3-C5 alkynylene,

[0308] Among them, R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 Heteroalkenyl, C2-C3-alkylene containing S or O, having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0309] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0310] A1 and / or A2 are C1-C5 alkyl, =O, -C0-C5 alkylene-hydroxy, -C(=O)N(R 15 )2-substituted C3-C7 cyclic hydrocarbon group containing 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, an 8- to 10-membered bicyclic heteroaryl group containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, optionally substituted by C1-C5 alkyl, hydroxyl, or Substituted C1-C5 alkyl, C2-C5 alkenyl, C3-C5 alkynyl, C1-C5 alkylene, C2-C5 alkenylene, C3-C5 alkynylene, wherein R 15 Each is independently H or C1-C3 alkyl, and d is 0, 1, 2, 3, 4 or 5.

[0311] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0312] A1 and / or A2 are

[0313] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0314] A1 and / or A2 can also be

[0315] Wherein, a is 1, 2, 3, 4 or 5;

[0316] Preferably, a is 1, 2 or 3.

[0317] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0318] A3 is the key.

[0319] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0320] A3 is a C1, C2, C3, C4, or C5 alkylene group.

[0321] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0322] A3 is a C1-C5 alkylene group, or a C2-C5 alkenylene group having 1 or 2 double bonds, or a C2-C5 alkynylene group having 1 or 2 triple bonds.

[0323] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0324] A3 is an unsubstituted C1-C5 alkylene group, or an unsubstituted C2-C5 alkenylene group, or an unsubstituted C3-C5 alkynylene group.

[0325] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0326] A3 is a substituted C1-C5 alkylene group, a substituted C2-C5 alkenylene group, or a substituted C3-C5 alkynylene group.

[0327] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0328] A3 is hydroxy, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、-R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C5 alkylene, C2-C5 alkenylene, C3-C5 alkynylene,

[0329] in,

[0330] R 13 Each independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0331] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0332] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0333] When A3 is -R 14 、-R 13 OR 14 、-R13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When the substituted C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene group is R 13 and / or R 14 It can be connected to the C atom on A3 to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0334] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0335] When the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 and A2 together with the nitrogen atom to which they are commonly attached form a nitrogen-containing three-membered, four-membered, five-membered, six-membered, seven-membered or eight-membered heterocyclic ring.

[0336] In some embodiments, A1 and A2 together with the nitrogen atom to which they are attached form a three-membered, four-membered, five-membered, or six-membered N-containing heterocyclic ring.

[0337] In some embodiments, A1 and A2 together with the nitrogen atom to which they are attached form a N-containing four-membered, five-membered, or six-membered heterocyclic ring.

[0338] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0339] When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 and A3 together with the nitrogen atom to which they are commonly attached form a nitrogen-containing three-, four-, five-, six-, seven-, or eight-membered heterocyclic ring.

[0340] In some embodiments, A1 and A3 together with the nitrogen atom to which they are attached form a N-containing three-membered, four-membered, five-membered, or six-membered heterocyclic ring.

[0341] In some embodiments, A1 and A3 together with the nitrogen atom to which they are attached form a N-containing four-membered, five-membered, or six-membered heterocyclic ring.

[0342] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0343] for

[0344] Wherein, c is 1, 2, 3, 4 or 5;

[0345] Preferably, c is 2, 3 or 4;

[0346] Preferably, c is 2 or 3.

[0347] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0348] A4 is a key.

[0349] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0350] A4 is a C1, C2, C3, C4, or C5 alkylene group.

[0351] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0352] A4 is a C1-C5 alkylene group, or a C2-C5 alkenylene group having 1 or 2 double bonds, or a C2-C5 alkynylene group having 1 or 2 triple bonds.

[0353] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0354] A4 is an unsubstituted C1-C5 alkylene group, or an unsubstituted C2-C5 alkenylene group, or an unsubstituted C3-C5 alkynylene group.

[0355] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0356] A4 is a substituted C1-C5 alkylene group, a substituted C2-C5 alkenylene group, or a substituted C3-C5 alkynylene group.

[0357] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0358] A4 is hydroxy, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C5 alkylene, C2-C5 alkenylene, C3-C5 alkynylene,

[0359] in,

[0360] R 13 Each independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0361] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0362] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0363] When A4 is -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When the substituted C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene group is R 13 and / or R 14 It can be connected to the C atom on A4 to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0364] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0365] A5, A6, A7, A8 and A 12 Each independently C1-C 18 alkylene group or bond.

[0366] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0367] A5, A6, A7, A8 and A 12 Each independently is 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 alkylene group or bond.

[0368] In some embodiments, A5, A6, A7, A8 and A 12 Each is independently a bond.

[0369] In other embodiments, A5, A6, A7, A8 and A 12 Each independently is 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 Hydrocarbylene.

[0370] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0371] A5, A6, A7, A8 and A 12 Each independently is C1-C 18 Alkylene, or C2-C 18 Alkenylene, or C2-C 18 Alkynylidene.

[0372] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0373] A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Hydrocarbylene.

[0374] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0375] A 12 is a bond, and A5 and A6 are not C1 alkylene groups at the same time.

[0376] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0377] A7 and A8 are each independently a C1, C2, C3, C4, C5, C6, C7 alkylene group or a bond.

[0378] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0379] A 12 is C1 alkylene, A5 is C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 alkylene; or A 12 is C1 alkylene, A6 is C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Hydrocarbylene.

[0380] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0381] A5 and / or A6 are unsubstituted C1-C 12 Alkylene, or unsubstituted C2-C 12 Alkenylene, or unsubstituted C3-C 12 For example, A5 and / or A6 are unsubstituted C1-C 12Alkylene, or unsubstituted C3-C9 alkylene, or unsubstituted C4-C9 alkylene, or unsubstituted C5-C8 alkylene, or unsubstituted C8 alkylene.

[0382] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0383] A5 and / or A6 is substituted C1-C 12 Alkylene, or substituted C2-C 12 Alkenylene, or substituted C3-C 12 For example, A5 and / or A6 are substituted C1-C 12 Alkylene, or substituted C3-C9 alkylene, or substituted C4-C9 alkylene, or substituted C5-C8 alkylene, or substituted C8 alkylene.

[0384] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0385] A7 and / or A8 are unsubstituted C1-C 12 Alkylene, or unsubstituted C2-C 12 Alkenylene, or unsubstituted C3-C 12 For example, A7 and / or A8 are unsubstituted C1-C5 alkylene, or unsubstituted C2-C4 alkylene, or unsubstituted C3 alkylene.

[0386] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0387] A7 and / or A8 are substituted C1-C 12 Alkylene, or substituted C2-C 12 Alkenylene, or substituted C3-C 12 For example, A7 and / or A8 is a substituted C1-C5 alkylene, a substituted C2-C4 alkylene, or a substituted C3 alkylene.

[0388] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0389] A 12 For unsubstituted C1-C 12 Alkylene, or unsubstituted C2-C12 Alkenylene, or unsubstituted C3-C 12 Alkynylidene. For example, A 12 It is an unsubstituted C1-C5 alkylene group or an unsubstituted C1-C3 alkylene group.

[0390] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0391] A 12 For the substituted C1-C 12 Alkylene, or substituted C2-C 12 Alkenylene, or substituted C3-C 12 Alkynylidene. For example, A 12 It is a substituted C1-C5 alkylene group or a substituted C1-C3 alkylene group.

[0392] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0393] A5, A6, A7, A8 and A 12 At least one of them is hydroxyl, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C 12 Alkylene, C2-C 12 Alkenylene, C3-C 12 Alkynylidene,

[0394] in,

[0395] R 13 Each independently C1-C12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0396] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0397] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0398] When A5, A6, A7, A8 and A 12 At least one of them is -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C 12 Alkylene, C2-C 12 Alkenylene, C3-C12 When alkynylene, R 13 and / or R 14 Can be replaced with A5, A6, A7, A8 or A 12 The C atoms on the alkyl group are connected to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0399] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0400] A9 is the key.

[0401] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0402] A9 is C1, C2, C3, C4, C5, C6, C7, C8 alkylene or C1, C2, C3, C4, C5, C6, C7, C8 heteroalkylene.

[0403] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0404] A9 is a C1-C8 alkylene group, or a C2-C8 alkenylene group having 1, 2 or more double bonds, or a C2-C8 alkynylene group having 1, 2 or more triple bonds.

[0405] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0406] Each A9 is independently an unsubstituted C1-C8 alkylene group, or an unsubstituted C2-C8 alkenylene group, or an unsubstituted C3-C8 alkynylene group.

[0407] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0408] At least one of A9 is a substituted C1-C8 alkylene group, a substituted C2-C8 alkenylene group, or a substituted C3-C8 alkynylene group.

[0409] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0410] At least one of A9 is hydroxy, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C8 alkylene, C2-C8 alkenylene, C3-C8 alkynylene,

[0411] in,

[0412] R 13 Each independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0413] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0414] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0415] When A9 is -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When the substituted C1-C8 alkylene, C2-C8 alkenylene, or C3-C8 alkynylene group is R 13 and / or R 14 It can be connected to the C atom on the substituted A9 to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0416] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0417] A 10 and A 11 Each is independently a C1, C2, C3, C4, C5, C6, C7, C8 hydrocarbon group, or a C1, C2, C3, C4, C5, C6, C7, C8 heterohydrocarbon group.

[0418] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0419] Each A 10 and each A 11 Each is independently a C1-C8 alkyl group, or a C2-C8 alkenyl group having 1, 2 or more double bonds, or a C2-C8 alkynyl group having 1, 2 or more triple bonds.

[0420] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0421] Each A 10 and / or each A 11 is an unsubstituted C1-C8 alkyl group, or an unsubstituted C2-C8 alkenyl group, or an unsubstituted C3-C8 alkynyl group.

[0422] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0423] Each A 10 and / or each A 11 At least one of them is a substituted C1-C8 alkyl, or a substituted C2-C8 alkenyl, or a substituted C3-C8 alkynyl.

[0424] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0425] Each A 10 and / or each A 11 At least one of them is hydroxyl, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C8 alkyl, C2-C8 alkenyl, C3-C8 alkynyl,

[0426] in,

[0427] R 13 Each independently C1-C 12Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0428] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0429] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0430] When A 10 and / or A 11 For the -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When the substituted C1-C8 alkyl, C2-C8 alkenyl, or C3-C8 alkynyl group, R 13 and / or R 14Can be replaced with A 10 or A 11 The C atoms on the alkyl group are connected to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0431] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R5 is an unsubstituted C1-C8 alkyl, or an unsubstituted C2-C8 alkenyl, or an unsubstituted C2-C8 alkynyl.

[0432] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R5 is a substituted C1-C8 alkyl, or a substituted C2-C8 alkenyl, or a substituted C2-C8 alkynyl.

[0433] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0434] R5 is hydroxy, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 substituted C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl,

[0435] in,

[0436] R 13 Each independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0437] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0438] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0439] When R5 is 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When the substituted C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl group, R 13 and / or R 14 It can be connected to the C atom on R5 to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0440] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0441] Y1 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)‐, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -S C(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 ), -C(=S)O-, -OC(=S)-, -C(=S)‐, -C(=S)S-, -SC(=S)-, -C(=S)N(R6)-, -N(R6)C(=S)-, -OC(=S)O-, -OC(=S)S-, -SC(=S) O-, -SC(=S)S-, -N(R6)C(=S)O-, -OC(=S)N(R6)-, -N(R6)C(=S)N(R6)-, -SC(=S)N(R6)-, -N(R6)C(=S)S-, -N(C(=S)A9OA 10 )-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2--OP(=O)O-, -OP(= O)(OH)O-, -OP(=O)(H)O-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S- or -SC(=O)O-.

[0442] In some embodiments, Y1 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A 11 ), -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OS(=O)2O-, -OS(=O)O-, -OP(= O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S- or -SC(=O)O-.

[0443] In some embodiments, Y1 is -N(H)C(=O)N(H)-, -S-, -OC(=O)O-, -N(H)C(=O)O-, -OC(=O)N(H)-, -C(=O)O-, -OC(=O)-, -N((CH2)3C(=O)OC5H 11 )C(=O)O-, -OC(=O)N((CH2)3C(=O)OC5H 11 )-, -N(H)C(=O)-, -C(=O)N(H)-, -N(C(=O)(CH2)3OC8H 17 ), -N(C(=O)CH2OCH3), -N(C(=O)CH3), -N(C(=O)C3H7), -N(C3H7)C(=O)O-, -OC(=O)N(C6H 13)-, -C(=O)N(C4H9)-, -N(CH(CH3)2)C(=O)-, -N((CH2)3C(=O)OC2H5)C(=O)O-, -N((CH2)3 C(=O)OCH2CH=CHC3H7)C(=O)O-, -N(C4H9)C(=O)-, -O-, -S(=O)2O-, -OS(=O)2-, -OS(=O)2O -, -OS(=O)O-, -S(=O)2NH-, -NHS(=O)2-, -OS(=O)2NH-, -NHS(=O)2NH-, -OP(=O)(H)O-, -OP (=O)(OH)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)N(H)-, -N(H)C(=O)S-, -C(=O)S- or -SC(=O)-.

[0444] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0445] Y1 is -C(=O)O-, -C(=O)‐, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, - OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N( R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 ), -C(=S)O-, -OC(=S)-, -C(=S)‐, -C(=S)S-, -SC(=S)-, -C(=S)N(R6)-, -N(R6)C(=S)-, -OC(=S)O-, -OC(=S)S-, -SC(=S) O-, -SC(=S)S-, -N(R6)C(=S)O-, -OC(=S)N(R6)-, -N(R6)C(=S)N(R6)-, -SC(=S)N(R6)-, -N(R6)C(=S)S-, -N(C(=S)A9OA 10)-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP(=O)O-, -OP(= O)(OH)O-, -OP(=O)(H)O-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S- or -SC(=O)O-.

[0446] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0447] Z1 is -C(=O)O-, -O-, -C(=O)‐, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O) O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-.

[0448] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0449] Z2 is -C(=O)O-, -O-, -C(=O)‐, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O) O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-.

[0450] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0451] R1 and R2 are each independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 、C 19 、C 20 、C 21 、C 22 、C 23 、C 24 Hydrocarbon, 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 、C22 、C 23 、C 24 Heteroalkyl.

[0452] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0453] R1 and / or R2 are C1-C 24 Alkyl groups (e.g. C5-C 16 Alkyl, C6-C 14 Alkyl, C6-C 12 alkyl), C2-C 24 Alkenyl (e.g. C5-C 16 Alkenyl, C6-C 14 Alkenyl, C6-C 12 alkenyl), C2-C 24 Alkynyl (e.g. C5-C 16 Alkynyl, C6-C 14 Alkynyl, C6-C 12 alkynyl).

[0454] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0455] R1 and / or R2 are unsubstituted C1-C 24 Alkyl (e.g. unsubstituted C5-C 16 Alkyl, unsubstituted C6-C 14 Alkyl, unsubstituted C6-C 12 alkyl), unsubstituted C2-C 24 Alkenyl (e.g., unsubstituted C5-C 16 Alkenyl, unsubstituted C6-C 14 Alkenyl, unsubstituted C6-C 12 alkenyl), unsubstituted C2-C 24 Alkynyl (e.g., unsubstituted C5-C 16 Alkynyl, unsubstituted C6-C 14 Alkynyl, unsubstituted C6-C 12 alkynyl).

[0456] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0457] R1 and / or R2 are substituted C1-C 24 Alkyl (e.g. substituted C5-C16 Alkyl, substituted C6-C 14 Alkyl, substituted C6-C 12 alkyl), substituted C2-C 24 Alkenyl (e.g. substituted C5-C 16 Alkenyl, substituted C6-C 14 Alkenyl, substituted C6-C 12 alkenyl), substituted C2-C 24 Alkynyl (e.g. substituted C5-C 16 Alkynyl, substituted C6-C 14 Alkynyl, substituted C6-C 12 Alkynyl, substituted C 10 alkynyl).

[0458] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0459] R1 and R2 are each independently C1-C 24 A straight-chain alkyl group, or a C2-C 24 a straight-chain alkenyl group, or a C2-C 24 A straight-chain alkynyl group, or a C1-C 24 A straight-chain heteroalkyl group, or a C2-C 24 a straight-chain heteroalkenyl group, or a C2-C 24 A straight-chain heteroalkynyl group.

[0460] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0461] R1 and R2 are each independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 、C 19 、C 20 、C 21 、C 22 、C 23 、C24 Straight chain alkyl, or 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 、C 24 Straight chain alkenyl, or 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 、C 24 A straight chain alkynyl, 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 、C 24 Straight chain heteroalkyl, or 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 、C22 、C 23 、C 24 A straight chain heteroalkenyl, or 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 、C 24 A straight-chain heteroalkynyl group.

[0462] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0463] R1 and R2 are each independently C3-C 24 Branched alkyl, or C3-C 24 Branched alkenyl, or C4-C4 having 1, 2, 3, 4 or more triple bonds 24 Branched alkynyl, or C3-C containing O or S 24 Branched heteroalkyl, or C3-C3 containing O or S with 1, 2, 3, 4 or more double bonds 24 branched heteroalkenyl, or C4-C4 containing O or S with 1, 2, 3, 4 or more triple bonds 24 Branched heteroalkynyl.

[0464] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0465] R1 and R2 are each independently 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 、C23 、C 24 Branched alkyl, or 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 、C 24 Branched alkenyl, or 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 、C 24 Branched alkynyl, or 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 、C 24 Branched heteroalkyl, or 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 、C 24 Branched heteroalkenyl, or 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 、C 24 Branched heteroalkynyl.

[0466] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0467] R8 and R 10 Each independently is 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 、C 24 Hydrocarbon, 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 、C 24 Heteroalkyl.

[0468] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0469] R8 and / or R 10 C1-C 20 Alkyl groups (e.g. C2-C 10 Alkyl, C2-C8 alkyl, C7-C 18 Alkyl), or C1-C 16 Alkenyl (e.g. C5-C 12 alkenyl, C5-C8 alkenyl, C5 alkenyl, C6 alkenyl), or C5-C 16 Alkynyl (e.g. C5-C 12 Alkynyl, C 10 alkynyl).

[0470] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0471] R8 and / or R 10 For unsubstituted C1-C 20 Alkyl (e.g. unsubstituted C2-C 10 Alkyl, unsubstituted C2-C8 alkyl, unsubstituted C7-C 18 alkyl), or unsubstituted C1-C 16 Alkenyl (e.g., unsubstituted C5-C 12 unsubstituted C5-C8 alkenyl, unsubstituted C5 alkenyl, unsubstituted C6 alkenyl), or unsubstituted C5-C 16 Alkynyl (e.g., unsubstituted C5-C 12 Alkynyl, unsubstituted C 10 alkynyl).

[0472] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0473] R8 and / or R 10 For the substituted C1-C 20 Alkyl groups (e.g. substituted C2-C 10 Alkyl, substituted C2-C8 alkyl, substituted C7-C 18 alkyl), or substituted C1-C 16 Alkenyl (e.g. substituted C5-C 12 alkenyl, substituted C5-C8 alkenyl, substituted C5 alkenyl, substituted C6 alkenyl), or substituted C5-C16 Alkynyl (e.g. substituted C5-C 12 Alkynyl, substituted C 10 alkynyl).

[0474] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0475] R8 and R 10 Each independently C1-C 24 A straight-chain alkyl group, or a C2-C 24 a straight-chain alkenyl group, or a C2-C 24 A straight-chain alkynyl group, or a C1-C 24 A straight-chain heteroalkyl group, or a C2-C 24 a straight-chain heteroalkenyl group, or a C2-C 24 A straight-chain heteroalkynyl group.

[0476] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0477] R8 and R 10 Each independently is 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 、C 24 Straight chain alkyl, or C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 、C 19 、C20 、C 21 、C 22 、C 23 、C 24 Straight chain alkenyl, or 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 、C 24 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 、C 24 Straight chain heteroalkyl, or 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 、C 24 A straight chain heteroalkenyl, or C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C18 、C 19 、C 20 、C 21 、C 22 、C 23 、C 24 A straight-chain heteroalkynyl group.

[0478] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0479] R8 and R 10 Each independently C3-C 24 Branched alkyl, or C3-C 24 Branched alkenyl, or C4-C4 having 1, 2, 3, 4 or more triple bonds 24 Branched alkynyl, or C3-C containing O or S 24 Branched heteroalkyl, or C3-C3 containing O or S with 1, 2, 3, 4 or more double bonds 24 branched heteroalkenyl, or C4-C4 containing O or S with 1, 2, 3, 4 or more triple bonds 24 Branched heteroalkynyl.

[0480] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0481] R8 and R 10 Each independently is 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 、C 24 Branched alkyl, or C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C18 、C 19 、C 20 、C 21 、C 22 、C 23 、C 24 Branched alkenyl, or 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 、C 24 Branched alkynyl, or 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 、C 24 Branched heteroalkyl, or 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 、C 24 Branched heteroalkenyl, or C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C16 、C 17 、C 18 、C 19 、C 20 、C 21 、C 22 、C 23 、C 24 Branched heteroalkynyl.

[0482] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0483] R8 and / or R 10 is hydroxyl, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C 20 Alkyl groups (e.g. substituted C2-C 10 Alkyl, substituted C2-C8 alkyl, substituted C7-C 18 Alkyl), C1-C 16 Alkenyl (e.g. substituted C5-C 12 alkenyl, substituted C5-C8 alkenyl, substituted C5 alkenyl, substituted C6 alkenyl), C5-C 16 Alkynyl (e.g. substituted C5-C 12 Alkynyl, substituted C 10 alkynyl),

[0484] in,

[0485] R 13 Each independently C1-C 12 Alkylene, C2-C12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0486] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0487] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0488] When R8 and / or R 10 Each independently by -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When substituted, R 13 and / or R 14 Can be used with the replaced R8 or R 10 The C atoms on the alkyl group are connected to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0489] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R8 and / or R 10 Each is independently substituted aryl. In some embodiments, R8 or R 10 is a phenyl group substituted by an alkyl group, for example:

[0490] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0491] R8 and R 10 Each independently

[0492] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0493] R6 is each independently a C1, C2, C3, C4, C5, C6, C7, C8 hydrocarbon group, or a C1, C2, C3, C4, C5, C6, C7, C8 heterohydrocarbon group.

[0494] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0495] R6 is each independently a C1-C8 alkyl group, or a C2-C8 alkenyl group having 1, 2 or more double bonds, or a C2-C8 alkynyl group having 1, 2 or more triple bonds.

[0496] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0497] R6 is each independently C1, C2, C3, C4, C5, C6, C7 or C8 alkyl.

[0498] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0499] Each R6 is each independently unsubstituted C1-C8 alkyl, or unsubstituted C2-C8 alkenyl, or unsubstituted C2-C8 alkynyl, or unsubstituted C1-C8 heteroalkyl, or unsubstituted C2-C8 heteroalkenyl, or unsubstituted C2-C8 heteroalkynyl. For example, R6 is each independently unsubstituted C1-C5 alkyl, unsubstituted C1-C3 alkyl, or unsubstituted C1 alkyl.

[0500] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0501] At least one of each R6 is a substituted C1-C8 alkyl group, or a substituted C2-C8 alkenyl group, or a substituted C2-C8 alkynyl group. For example, one of each R6 is a substituted C1-C5 alkyl group, a substituted C1-C3 alkyl group, or a substituted C3 alkyl group.

[0502] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0503] At least one of each R6 is hydroxy, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl,

[0504] in,

[0505] R 13 Each independently C1-C 12 Alkylene, C2-C 12Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0506] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0507] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0508] When R6 is -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When the substituted C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl group, R 13 and / or R 14 It can be connected to the C atom on the substituted R6 to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0509] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0510] A 13 and A 14 Each is independently C1, C2, C3, C4, C5, C6, C7, C8 alkylene, or C1, C2, C3, C4, C5, C6, C7, C8 heteroalkylene, or a bond.

[0511] In some embodiments, A 13 and A 14 Each is independently a bond.

[0512] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0513] A 13 and A 14 Each is independently a C1-C8 alkylene group, or a C2-C8 alkenylene group having 1, 2 or more double bonds, or a C2-C8 alkynylene group having 1, 2 or more triple bonds, or a bond.

[0514] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0515] Each A 13 and each A 14 Each is independently a C1-C8 alkylene group, a C2-C8 alkenylene group, or a C2-C8 alkynylene group.

[0516] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0517] Each A 13 and / or each A 14 is an unsubstituted C1-C8 alkylene group, or an unsubstituted C2-C8 alkenylene group, or an unsubstituted C2-C8 alkynylene group. For example, A 13 and A 14 Each is independently an unsubstituted C2-C5 alkylene group or an unsubstituted C3-C4 alkylene group.

[0518] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0519] Each A13 and / or each A 14 At least one of them is a substituted C1-C8 alkylene group, a substituted C2-C8 alkenylene group, or a substituted C2-C8 alkynylene group.

[0520] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0521] Each A 13 and / or each A 14 At least one of them is hydroxyl, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C8 alkylene, C2-C8 alkenylene, C2-C8 alkynylene,

[0522] in,

[0523] R 13 Each independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0524] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0525] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: 13 and / or A 14 For the -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 When the substituted C1-C8 alkylene, C2-C8 alkenylene, or C2-C8 alkynylene group is R 13 and / or R 14 Can be replaced with A 13 or A 14 The C atoms on the alkyl group are connected to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0526] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0527] R9 and R 11 Each independently is 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 、C 24 Hydrocarbon, 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 、C 24 Heteroalkyl.

[0528] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0529] Each R9 is independently C1-C 12 Alkyl (e.g. C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl), C5-C 16 Alkenyl (e.g. C5-C 12 alkenyl, C5-C8 alkenyl, C6 alkenyl), C5-C 16 Alkynyl (e.g. C9-C 11 Alkynyl, C 10 alkynyl).

[0530] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0531] Each R9 is an unsubstituted C1-C 12 Alkyl (e.g., unsubstituted C3-C9 alkyl, unsubstituted C5-C8 alkyl, unsubstituted C6 alkyl, unsubstituted C7 alkyl), unsubstituted C5-C 16 Alkenyl (e.g. unsubstituted C5-C 12 alkenyl, unsubstituted C5-C8 alkenyl, unsubstituted C6 alkenyl), unsubstituted C5-C 16 Alkynyl (e.g., unsubstituted C9-C 11 Alkynyl, unsubstituted C10 alkynyl).

[0532] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0533] At least one of each R9 is a substituted C1-C 12 Alkyl (e.g., substituted C3-C9 alkyl, substituted C5-C8 alkyl, substituted C6 alkyl, substituted C7 alkyl), substituted C5-C 16 Alkenyl (e.g. substituted C5-C 12 alkenyl, substituted C5-C8 alkenyl, substituted C6 alkenyl), substituted C5-C 16 Alkynyl (e.g. substituted C9-C 11 Alkynyl, substituted C 10 alkynyl).

[0534] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0535] Each R 11 Each independently is C1-C 12 Alkyl (e.g. C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl), C5-C 16 Alkenyl (e.g. C5-C 12 alkenyl, C5-C8 alkenyl, C6 alkenyl), C5-C 16 Alkynyl (e.g. C9-C 11 Alkynyl, C 10 alkynyl).

[0536] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0537] Each R 11 For unsubstituted C1-C 12 Alkyl (e.g., unsubstituted C3-C9 alkyl, unsubstituted C5-C8 alkyl, unsubstituted C6 alkyl, unsubstituted C7 alkyl), unsubstituted C5-C 16 Alkenyl (e.g. unsubstituted C5-C 12 alkenyl, unsubstituted C5-C8 alkenyl, unsubstituted C6 alkenyl), unsubstituted C5-C 16 Alkynyl (e.g., unsubstituted C9-C 11 Alkynyl, unsubstituted C 10 alkynyl).

[0538] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0539] Each R 11 At least one of them is substituted C1-C 12 Alkyl (e.g., substituted C3-C9 alkyl, substituted C5-C8 alkyl, substituted C6 alkyl, substituted C7 alkyl), substituted C5-C 16 Alkenyl (e.g. substituted C5-C 12 alkenyl, substituted C5-C8 alkenyl, substituted C6 alkenyl), substituted C5-C 16 Alkynyl (e.g. substituted C9-C 11 Alkynyl, substituted C 10 alkynyl).

[0540] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0541] R9 and R 11 Each independently C1-C 24 A straight-chain alkyl group, or a C2-C 24 a straight-chain alkenyl group, or a C2-C 24 A straight-chain alkynyl group, or a C1-C 24 A straight-chain heteroalkyl group, or a C2-C 24 a straight-chain heteroalkenyl group, or a C2-C 24 A straight-chain heteroalkynyl group.

[0542] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0543] R9 and R 11 Each independently is 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 、C 24 Straight chain alkyl, or 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 、C 24 Straight chain alkenyl, or 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 、C 24 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 、C 24 Straight chain heteroalkyl, or C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C17 、C 18 、C 19 、C 20 、C 21 、C 22 、C 23 、C 24 A straight chain heteroalkenyl, or 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 、C 24 A straight-chain heteroalkynyl group.

[0544] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0545] R9 and R 11 Each independently C3-C 24 Branched alkyl, or C3-C 24 Branched alkenyl, or C4-C4 having 1, 2, 3, 4 or more triple bonds 24 Branched alkynyl, or C3-C containing O or S 24 Branched heteroalkyl, or C3-C3 containing O or S with 1, 2, 3, 4 or more double bonds 24 branched heteroalkenyl, or C4-C4 containing O or S with 1, 2, 3, 4 or more triple bonds 24 Branched heteroalkynyl.

[0546] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0547] R9 and R 11 Each independently is 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 、C 24 Branched alkyl, or 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 、C 24 Branched alkenyl, or 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 、C 24 Branched alkynyl, or 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 、C 24 Branched heteroalkyl, or C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C15 、C 16 、C 17 、C 18 、C 19 、C 20 、C 21 、C 22 、C 23 、C 24 Branched heteroalkenyl, or 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 、C 24 Branched heteroalkynyl.

[0548] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0549] Each R9 and / or each R 11 At least one of them is hydroxyl, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C 12 Alkyl (C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl), C5-C 16 Alkenyl (e.g. C5-C12 alkenyl, C5-C8 alkenyl, C6 alkenyl), substituted C5-C 16 Alkynyl (e.g. C9-C 11 Alkynyl, C 10 alkynyl),

[0550] in,

[0551] R 13 Each independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0552] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0553] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0554] When R9 and / or R 11 For the -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C 12 Alkyl (C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl), C5-C 16 Alkenyl (e.g. C5-C 12 alkenyl, C5-C8 alkenyl, C6 alkenyl), substituted C5-C 16 Alkynyl (e.g. C9-C 11 Alkynyl, C 10 Alkynyl), R 13 and / or R 14 Can be replaced with R9 or R 11 The C atoms on the alkyl group are connected to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0555] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R9 and / or each R 11 In some embodiments, at least one of R9 and R 11 is a phenyl group substituted by an alkyl group, for example:

[0556] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0557] R9 and R 11 Each independently

[0558] Preferably

[0559] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0560] Z8 are each independently a bond.

[0561] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0562] Z9 are each independently a bond.

[0563] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0564] R1 is H, C1-C 24 Hydrocarbon, C1-C 24 heteroalkyl, Z6R8 or -CH(OR9)2.

[0565] In some embodiments, R1 is -CH(OR9)2.

[0566] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0567] R2 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z7R 10 or-CH(OR 11 )2.

[0568] In some embodiments, R2 is -CH(OR 11 )2.

[0569] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0570] R1 and / or R2 are hydroxyl, halogen, =O, =S, cyano, cycloalkyl, aryl, heterocycle, -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14 , ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C 24 Alkyl groups (e.g. C5-C 16Alkyl, C6-C 14 Alkyl, C6-C 12 alkyl), C2-C 24 Alkenyl (e.g. C5-C 16 Alkenyl, C6-C 14 Alkenyl, C6-C 12 alkenyl), C2-C 24 Alkynyl (e.g. C5-C 16 Alkynyl, C6-C 14 Alkynyl, C6-C 12 Alkynyl, C 10 alkynyl),

[0571] in,

[0572] R 13 Each independently C1-C 12 Alkylene, C2-C 12 Alkenylene, C2-C 12 Alkynylidene, C1-C containing S or O 12 Heteroalkylene, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenylene, or C2-C2-alkylene containing S or O having 1, 2, 3 or more triple bonds 12 heteroalkynylene;

[0573] R 14 Each independently represents H, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0574] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0575] When R1 and / or R2 are each independently replaced by -R 14 、-R 13 OR 14 、-R 13 SR 14、 -R 13 OC(=O)OR 14, ‐R 13 OC(=O)SR 14 , ‐R 13 C(=O)N(R 14 )2. -R 13 OC(=O)R 14 , ‐R 13 SC(=O)OR 14 , ‐R 13 N(R 14 )C(=O)R 14 or -R 13 C(=O)OR 14 Substituted C1-C 24 Alkyl groups (e.g. C5-C 16 Alkyl, C6-C 14 Alkyl, C6-C 12 alkyl), C2-C 24 Alkenyl (e.g. C5-C 16 Alkenyl, C6-C 14 Alkenyl, C6-C 12 alkenyl), C2-C 24 Alkynyl (e.g. C5-C 16 Alkynyl, C6-C 14 Alkynyl, C6-C 12 Alkynyl, C 10 Alkynyl), R 13 and / or R 14 It can be connected to the C atom on the substituted R1 or R2 to form a three-membered ring, a four-membered ring, a five-membered ring or a six-membered ring.

[0576] In some embodiments, R 14 and R are independently substituted aryl, substituted cycloalkyl or substituted heterocyclic. 14 In some embodiments, R 14 is a phenyl group substituted by an alkyl group, for example:

[0577] In some embodiments, R 14 is an unsubstituted cycloalkyl group, for example, cyclobutyl, cyclopentyl or cyclohexyl.

[0578] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0579] R1 and R2 are each independently a C5-C 16 Alkyl, for example, C6-C 14Alkyl, C6-C substituted by hydroxyl 12 Alkyl, C substituted by hydroxy 10 In some embodiments, R1 and R2 are each independently C 10 Alkyl groups, such as:

[0580] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0581] R1 and R2 are each independently

[0582] Preferably:

[0583] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-I) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R1 is Z6R8 or -CH(OR9)2, R2 is Z7R 10 or-CH(OR 11 )2.

[0584] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has the structure represented by formula (II-Ia):

[0585] in,

[0586] A1 is H, C1-C5 hydrocarbon group or C1-C5 heterohydrocarbon group;

[0587] A2 is H, C1-C5 hydrocarbon group or C1-C5 heterohydrocarbon group;

[0588] A3 is a C1-C5 alkylene group or a bond;

[0589] A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R1, R2, and A 12 The definition of is as defined in formula (II-I).

[0590] The present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, when applicable, including one or more of the following features.

[0591] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0592] A1 and A2 are each independently H.

[0593] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0594] A1 and A2 are each independently a C1, C2, C3, C4, or C5 hydrocarbon group, or a C1, C2, C3, C4, or C5 heterohydrocarbon group.

[0595] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0596] A1 and A2 are each independently a C1-C5 alkyl group, or a C2-C5 alkenyl group having 1 or 2 double bonds, or a C2-C5 alkynyl group having 1 or 2 triple bonds, or a C1-C5 heteroalkyl group containing S or O, or a C2-C5 heteroalkenyl group containing S or O having 1 or 2 double bonds, or a C2-C5 heteroalkynyl group containing S or O having 1 or 2 triple bonds.

[0597] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0598] A1 and A2 are each independently optionally replaced by hydroxy, cyano, phenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5- to 6-membered monocyclic group, heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 8- to 10-membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, -OR 12 ,-C(=O)R 12 ,-C(=O)SR 12 ,-OC(=O)R 12 ,-OC(=O)OR 12 ,-N(R 12 )2,-C(=O)N(R 12 )2,-C(=S)N(R 12 )2,-S(=O)2R 12 ,-S(=O)2N(R 12 )2,-OC(=O)N(R 12 )2,-CH(NR 12 )N(R12 )2,-C(NR 12 )2R 12 ,-C(=O)N(R 12 )OR 12 ,-CH(R 12 )N(R 12 )2C(=O)OR 12 ,-C(R 12 )3,-N(R 12 )C(=O)R 12 ,-N(R 12 )C(=O)OR 12 ,-N(R 12 )S(=O)2R 12 ,-N(R 12 )C(=O)N(R 12 )2,-N(R 12 )C(=S)N(R 12 )2,-N(R 12 )C(NR 12 )N(R 12 )2,-N(R 12 )C(CHR 12 )N(R 12 )2,-N(OR 12 )C(=O)R 12 ,-N(OR 12 )S(=O)2R 12 ,-N(OR 12 )C(=O)OR 12 ,-N(OR 12 )C(=O)N(R 12 )2,-N(OR 12 )C(=S)N(R 12 )2,-N(OR 12 )C(NR 12 )N(R 12 )2,-N(OR 12 )C(CHR 12 )N(R 12 )2,-OP(=O)(OR 12 )2,-P(=O)(OR 12 )2, or a 3- to 7-membered alicyclic and 3- to 7-membered heterocyclic ring containing 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2,-C(=NO-CH3)N(R 12 )2,-C(=N-SO2-NH2)N(R 12 )2,-C(=CH-NO2)N(R12 )2 or -C(=O)OR 12 replace;

[0599] Among them, R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0600] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0601] A1 and A2 are each independently optionally substituted with C1-C5 alkyl, =O, -C0-C5 alkylene-hydroxy, -C(=O)N(R 15 )2-substituted C3-C7 cyclic hydrocarbon group containing 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, an 8- to 10-membered bicyclic heteroaryl group containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, optionally substituted by C1-C5 alkyl, hydroxyl, or Substituted, where R 15 Each is independently H or C1-C3 alkyl, and d is 0, 1, 2, 3, 4 or 5.

[0602] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0603] A1 and A2 are each independently

[0604] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0605] A1 and A2 can also be independently

[0606] Wherein, a is 1, 2, 3, 4 or 5;

[0607] Preferably, a is 1, 2 or 3.

[0608] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0609] A3 is the key.

[0610] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0611] A3 is a C1, C2, C3, C4, or C5 alkylene group.

[0612] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0613] A3 is a C1-C5 alkylene group, or a C2-C5 alkenylene group having 1 or 2 double bonds, or a C2-C5 alkynylene group having 1 or 2 triple bonds.

[0614] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ia) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0615] for

[0616] Wherein, c is 1, 2, 3, 4 or 5;

[0617] Preferably, c is 2, 3 or 4;

[0618] Preferably, c is 2 or 3.

[0619] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-Ib):

[0620] in,

[0621] A1 is a C1-C5 alkylene group or a C1-C5 heteroalkylene group;

[0622] A2 is a C1-C5 alkylene group or a C1-C5 heteroalkylene group;

[0623] A3 is a C1-C5 alkylene group or a bond;

[0624] A1 and A2 together with the nitrogen atom to which they are commonly attached form a nitrogen-containing heterocyclic ring;

[0625] A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R1, R2, and A 12 The definition of is as defined in formula (II-I).

[0626] The present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, when applicable, including one or more of the following features.

[0627] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0628] A1 and A2 are each independently a C1, C2, C3, C4, or C5 alkylene group, or a C1, C2, C3, C4, or C5 heteroalkylene group.

[0629] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0630] A1 and A2 are each independently C1-C5 alkylene, or C2-C5 alkenylene having 1 or 2 double bonds, or C2-C5 alkynylene having 1 or 2 triple bonds, or C1-C5 heteroalkylene containing S or O, or C2-C5 heteroalkenylene containing S or O having 1 or 2 double bonds, or C2-C5 heteroalkynylene containing S or O having 1 or 2 triple bonds.

[0631] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0632] A1 and A2 are each independently optionally replaced by hydroxy, cyano, phenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5- to 6-membered monocyclic group, heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 8- to 10-membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, -OR 12 ,-C(=O)R 12 ,-C(=O)SR 12 ,-OC(=O)R 12 ,-OC(=O)OR 12 ,-N(R 12 )2,-C(=O)N(R 12 )2,-C(=S)N(R12 )2,-S(=O)2R 12 ,-S(=O)2N(R 12 )2,-OC(=O)N(R 12 )2,-CH(NR 12 )N(R 12 )2,-C(NR 12 )2R 12 ,-C(=O)N(R 12 )OR 12 ,-CH(R 12 )N(R 12 )2C(=O)OR 12 ,-C(R 12 )3,-N(R 12 )C(=O)R 12 ,-N(R 12 )C(=O)OR 12 ,-N(R 12 )S(=O)2R 12 ,-N(R 12 )C(=O)N(R 12 )2,-N(R 12 )C(=S)N(R 12 )2,-N(R 12 )C(NR 12 )N(R 12 )2,-N(R 12 )C(CHR 12 )N(R 12 )2,-N(OR 12 )C(=O)R 12 ,-N(OR 12 )S(=O)2R 12 ,-N(OR 12 )C(=O)OR 12 ,-N(OR 12 )C(=O)N(R 12 )2,-N(OR 12 )C(=S)N(R 12 )2,-N(OR 12 )C(NR 12 )N(R 12 )2,-N(OR 12 )C(CHR 12 )N(R 12 )2,-OP(=O)(OR 12 )2,-P(=O)(OR 12)2, or a 3- to 7-membered alicyclic and 3- to 7-membered heterocyclic ring containing 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2,-C(=NO-CH3)N(R 12 )2,-C(=N-SO2-NH2)N(R 12 )2,-C(=CH-NO2)N(R 12 )2 or -C(=O)OR 12 replace;

[0633] Among them, R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0634] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0635] A3 is the key.

[0636] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0637] A3 is a C1, C2, C3, C4, or C5 alkylene group.

[0638] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0639] A3 is a C1-C5 alkylene group, or a C2-C5 alkenylene group having 1 or 2 double bonds, or a C2-C5 alkynylene group having 1 or 2 triple bonds.

[0640] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0641] A1 and A2 together with the nitrogen atom to which they are commonly attached form a nitrogen-containing three-membered, four-membered, five-membered, six-membered, seven-membered or eight-membered heterocyclic ring.

[0642] In some embodiments, A1 and A2 together with the nitrogen atom to which they are attached form a three-membered, four-membered, five-membered, or six-membered N-containing heterocyclic ring.

[0643] In some embodiments, A1 and A2 together with the nitrogen atom to which they are attached form a N-containing four-membered, five-membered, or six-membered heterocyclic ring.

[0644] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ib) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0645] for

[0646] Wherein, c is 1, 2, 3, 4 or 5;

[0647] Preferably, c is 2, 3 or 4;

[0648] Preferably, c is 2 or 3.

[0649] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-Ic):

[0650] in,

[0651] A1 is a C1-C5 alkylene group or a C1-C5 heteroalkylene group;

[0652] A2 is H, C1-C5 hydrocarbon group or C1-C5 heterohydrocarbon group;

[0653] A3 is a C1-C5 alkylene group;

[0654] A1 and A3 together with the nitrogen atom to which they are commonly attached form a nitrogen-containing heterocyclic ring;

[0655] A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R1, R2, and A 12 The definition of is as defined in formula (II-I).

[0656] The present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, when applicable, including one or more of the following features.

[0657] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0658] A2 is H.

[0659] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0660] A1 is a C1, C2, C3, C4, or C5 alkylene group, or a C1, C2, C3, C4, or C5 heteroalkylene group.

[0661] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0662] A1 is C1-C5 alkylene, or C2-C5 alkenylene having 1 or 2 double bonds, or C2-C5 alkynylene having 1 or 2 triple bonds, or C1-C5 heteroalkylene containing S or O, or C2-C5 heteroalkenylene containing S or O having 1 or 2 double bonds, or C2-C5 heteroalkynylene containing S or O having 1 or 2 triple bonds.

[0663] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0664] A2 is a C1, C2, C3, C4, or C5 hydrocarbon group, or a C1, C2, C3, C4, or C5 heterohydrocarbon group.

[0665] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0666] A2 is C1-C5 alkyl, or C2-C5 alkenyl having 1 or 2 double bonds, or C2-C5 alkynyl having 1 or 2 triple bonds, or C1-C5 heteroalkyl containing S or O, or C2-C5 heteroalkenyl containing S or O having 1 or 2 double bonds, or C2-C5 heteroalkynyl containing S or O having 1 or 2 triple bonds.

[0667] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0668] A1 and A2 are each independently optionally replaced by hydroxy, cyano, phenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5- to 6-membered monocyclic group, heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 8- to 10-membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, -OR 12 ,-C(=O)R 12 ,-C(=O)SR 12 ,-OC(=O)R 12 ,-OC(=O)OR 12 ,-N(R 12 )2,-C(=O)N(R 12 )2,-C(=S)N(R 12 )2,-S(=O)2R 12 ,-S(=O)2N(R 12 )2,-OC(=O)N(R 12 )2,-CH(NR 12 )N(R 12 )2,-C(NR 12 )2R 12 ,-C(=O)N(R 12 )OR 12 ,-CH(R 12 )N(R 12 )2C(=O)OR 12 ,-C(R 12 )3,-N(R 12 )C(=O)R 12 ,-N(R 12 )C(=O)OR 12 ,-N(R 12 )S(=O)2R 12 ,-N(R 12 )C(=O)N(R 12 )2,-N(R 12 )C(=S)N(R 12 )2,-N(R 12 )C(NR 12 )N(R 12 )2,-N(R 12 )C(CHR 12 )N(R 12 )2,-N(OR 12 )C(=O)R 12 ,-N(OR 12 )S(=O)2R 12 ,-N(OR 12 )C(=O)OR 12,-N(OR 12 )C(=O)N(R 12 )2,-N(OR 12 )C(=S)N(R 12 )2,-N(OR 12 )C(NR 12 )N(R 12 )2,-N(OR 12 )C(CHR 12 )N(R 12 )2,-OP(=O)(OR 12 )2,-P(=O)(OR 12 )2, or a 3- to 7-membered alicyclic and 3- to 7-membered heterocyclic ring containing 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2,-C(=NO-CH3)N(R 12 )2,-C(=N-SO2-NH2)N(R 12 )2,-C(=CH-NO2)N(R 12 )2 or -C(=O)OR 12 replace;

[0669] Among them, R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C 12 Alkenyl, C2-C 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C2 containing S or O, having 1, 2, 3 or more double bonds 12 heteroalkenyl, or C2-C2-alkyl containing S or O having 1, 2, 3 or more triple bonds 12 Heteroalkynyl.

[0670] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0671] A1 and A2 are each independently optionally substituted with C1-C5 alkyl, =O, -C0-C5 alkylene-hydroxy, -C(=O)N(R 15 )2-substituted C3-C7 cyclic hydrocarbon group containing 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, an 8- to 10-membered bicyclic heteroaryl group containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, optionally substituted by C1-C5 alkyl, hydroxyl, or Substituted, where R15 Each is independently H or C1-C3 alkyl, and d is 0, 1, 2, 3, 4 or 5.

[0672] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0673] A2 is

[0674] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0675] A2 can also be

[0676] Wherein, a is 1, 2, 3, 4 or 5;

[0677] Preferably, a is 1, 2 or 3.

[0678] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0679] A3 is a C1, C2, C3, C4, or C5 alkylene group.

[0680] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0681] A3 is a C1-C5 alkylene group, or a C2-C5 alkenylene group having 1 or 2 double bonds, or a C2-C5 alkynylene group having 1 or 2 triple bonds.

[0682] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0683] A1 and A3 together with the nitrogen atom to which they are commonly attached form a nitrogen-containing three-membered, four-membered, five-membered, six-membered, seven-membered or eight-membered heterocyclic ring.

[0684] In some embodiments, A1 and A3 together with the nitrogen atom to which they are attached form a N-containing three-membered, four-membered, five-membered, or six-membered heterocyclic ring.

[0685] In some embodiments, A1 and A3 together with the nitrogen atom to which they are attached form a N-containing four-membered, five-membered, or six-membered heterocyclic ring.

[0686] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-Ic) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

[0687] for

[0688] Wherein, c is 1, 2, 3, 4 or 5;

[0689] Preferably, c is 2, 3 or 4;

[0690] Preferably, c is 2 or 3.

[0691] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-Id):

[0692] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1, R2 and A 12 The definition of is as defined in formula (II-I).

[0693] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-Ie):

[0694] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1, R2 and A 12 The definition of is as defined in formula (II-I).

[0695] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has the structure represented by formula (II-II):

[0696] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R2, R9 and A 12 The definition of formula (II-

[0697] 1).

[0698] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-IIa):

[0699] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R2, R9 and A 12 The definition of is as defined in formula (II-I).

[0700] The present disclosure provides an amino lipid compound of formula (II-IIa) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, when applicable, including one or more of the following features.

[0701] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 or C 18 Hydrocarbylene.

[0702] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 or C 18 Alkylene.

[0703] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 or C 18 Alkenylene.

[0704] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16、C 17 or C 18 Alkynylidene.

[0705] In some embodiments, A5 and A6 are not both methylene.

[0706] In some embodiments, Z1 is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-.

[0707] In some embodiments, Z2 is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-.

[0708] In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6 alkylene or a bond.

[0709] In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6 alkylene or a bond.

[0710] In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6 alkenylene or a bond.

[0711] In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6 alkynylene or a bond.

[0712] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond.

[0713] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond.

[0714] In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond.

[0715] In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond.

[0716] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-IIb):

[0717] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R2, R9 and A 12 The definition of is as defined in formula (II-I).

[0718] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-III):

[0719] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R9, R 11 and A 12 The definition of is as defined in formula (II-I).

[0720] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-IIIa):

[0721] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, R 11 and A 12 The definition of is as defined in formula (II-I).

[0722] The present disclosure provides an amino lipid compound of formula (II-IIIa) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, when applicable, including one or more of the following features.

[0723] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 or C 18 Hydrocarbylene.

[0724] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 or C 18 Alkylene.

[0725] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 or C 18 Alkenylene.

[0726] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C16 、C 17 or C 18 Alkynylidene.

[0727] In some embodiments, A5 and A6 are not both methylene.

[0728] In some embodiments, Z1 is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-.

[0729] In some embodiments, Z2 is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-.

[0730] In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6 alkylene or a bond.

[0731] In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6 alkylene or a bond.

[0732] In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6 alkenylene or a bond.

[0733] In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6 alkynylene or a bond.

[0734] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond.

[0735] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond.

[0736] In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond.

[0737] In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond.

[0738] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-IIIb):

[0739] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, R 11 and A 12 The definition of is as defined in formula (II-I).

[0740] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-IVa) or (II-IVb):

[0741] Among them, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9, R 11 and A 12 The definition of is as defined in formula (II-I).

[0742] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-IVa) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0743] A1, A2, and A3 are one of the following:

[0744] (1) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, and A3 is C1-C5 alkylene or a bond;

[0745] (2) when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene or a bond, and A1 and A2 together with the nitrogen atom to which they are attached form a nitrogen-containing heterocyclic ring; or

[0746] (3) When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A3 is C1-C5 alkylene, and A1 and A3, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocycle;

[0747] (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene, and A1, A2 and A3, together with the nitrogen atom to which they are commonly attached, form a spirocyclic heterocycle, a fused heterocycle or a bridged heterocycle containing N;

[0748] A4 is a C1-C5 alkylene group or a bond;

[0749] A5, A6, A7, A8 and A 12 Each independently C1-C 18 Alkylidene, C1-C 18 heteroalkylene or bond;

[0750] Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0751] R6 are each independently H or C1-C8 hydrocarbon group;

[0752] Each R9 and each R 11 Each independently C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0753] each A9 is a C1-C8 alkylene group or a bond;

[0754] Each A 10 and each A 11 Each is independently a C1-C8 hydrocarbon group;

[0755] Preferably, the hydrocarbon group is an alkyl group, an alkenyl group or an alkynyl group;

[0756] Preferably, the hydrocarbylene group is an alkylene group, an alkenylene group or an alkynylene group;

[0757] Preferably, the heteroalkyl group is a heteroalkyl group, a heteroalkenyl group or a heteroalkynyl group;

[0758] Preferably, the heteroalkylene group is a heteroalkylene group, a heteroalkenylene group or a heteroalkynylene group.

[0759] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-Va), (II-Vb), (II-Vc), (II-Vd), (II-Ve), (II-Vf), (II-Vg), or (II-Vh):

[0760] Among them, A1, A2, A3, A4, A5, A6, A7, A8, R9, R 11 and A 12 The definition of is as defined in formula (II-I).

[0761] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIa):

[0762] in,

[0763] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1 and R2 are as defined in formula (II-I).

[0764] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0765] A1, A2, and A3 are one of the following:

[0766] (1) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, and A3 is C1-C5 alkylene or a bond;

[0767] (2) when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene or a bond, and A1 and A2 together with the nitrogen atom to which they are attached form a nitrogen-containing heterocyclic ring; or

[0768] (3) When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A3 is C1-C5 alkylene, and A1 and A3, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocycle;

[0769] (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene, and A1, A2 and A3, together with the nitrogen atom to which they are commonly attached, form a spirocyclic heterocycle, a fused heterocycle or a bridged heterocycle containing N;

[0770] A4 is a C1-C5 alkylene group or a bond;

[0771] A5, A6, A7 and A8 are each independently C1-C 18 Alkylidene, C1-C 18 heteroalkylene or bond;

[0772] Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0773] Y1 is -Z3C(=O)Z4-, -N(R5)-, -Z3C(=S)Z4-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP (=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -O-, -S-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S- or -SC(=O)O-;

[0774] X is C or N;

[0775] R1 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z6R8, -C(R6)(OA 13 Z8R9)2、-C(R6)(SA 13 Z8R9)2 or -C(R6)(SA 13 Z8R9)(OA 13 Z8R9);

[0776] R2 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z7R 10 、-C(R6)(OA 14 Z9R 11 )2、-C(R6)(SA 14 Z9R 11 )2 or -C(R6)(SA 14 Z9R 11 )(OA 14 Z9R 11 );

[0777] Z3 and Z4 are each independently -O-, -N(R6)-, -S- or a bond;

[0778] Z6 and Z7 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0779] R5 is -C(=O)A9Z5A 10 、-C(=O)A 11 , H or C1-C8 hydrocarbon group;

[0780] Z5 is -O- or ‐S‐;

[0781] Z8 and Z9 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S -, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(=O)2O- or bond;

[0782] R6 are each independently H or C1-C8 hydrocarbon group;

[0783] R8 and R 10 Each independently represents H, C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0784] Each R9 and each R 11 Each independently C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0785] each A9 is a C1-C8 alkylene group or a bond;

[0786] Each A 10 and each A 11 Each is independently a C1-C8 hydrocarbon group;

[0787] Each A 13 and each A 14 are each independently C1-C8 alkylene, C1-C8 heteroalkylene or a bond;

[0788] Preferably, the hydrocarbon group is an alkyl group, an alkenyl group or an alkynyl group;

[0789] Preferably, the hydrocarbylene group is an alkylene group, an alkenylene group or an alkynylene group;

[0790] Preferably, the heteroalkyl group is a heteroalkyl group, a heteroalkenyl group or a heteroalkynyl group;

[0791] Preferably, the heteroalkylene group is a heteroalkylene group, a heteroalkenylene group or a heteroalkynylene group.

[0792] In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 an alkylene group or a bond, and not a methylene group at the same time.

[0793] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond, and are not both methylene.

[0794] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkylene.

[0795] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Hydrocarbylene.

[0796] In some embodiments, A5 and A6 are each independently C 11 、C 12 、C 13 or C 14 Hydrocarbylene.

[0797] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C 17 or C 18 Hydrocarbylene.

[0798] In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 an alkylene group or a bond, and not a methylene group at the same time.

[0799] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond, and are not both methylene.

[0800] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkylene.

[0801] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Alkylene.

[0802] In some embodiments, A5 and A6 are each independently C 11 、C 12 、C 13 or C 14 Alkylene.

[0803] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C17 or C 18 Alkylene.

[0804] In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Alkenylene or bond.

[0805] In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond.

[0806] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkenylene.

[0807] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Alkenylene.

[0808] In some embodiments, A5 and A6 are each independently C 11 、C 12 、C 13 or C 14 Alkenylene.

[0809] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C 17 or C 18 Alkenylene.

[0810] In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 Alkynylene or bond.

[0811] In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond.

[0812] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkynylene.

[0813] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Alkynylidene.

[0814] In some embodiments, A5 and A6 are each independently C 11 、C 12 、C 13 or C 14 Alkynylidene.

[0815] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C 17 or C 18 Alkynylidene.

[0816] In some embodiments, A1 and A2 are each independently C1-C5 alkyl, preferably C1-C3 alkyl, such as methyl, ethyl, n-propyl or isopropyl; A3 is C1-C5 alkylene, preferably C2-C4 alkylene, such as -(CH2)2-, -(CH2)3-, -(CH2)4-; Y1 is -Z3C(=O)Z4-, preferably -N(R6)C(=O)N(R6)-, more preferably -N(H)C(=O)N(H)-; Z1 and Z2 are each independently -C(=O)O- or -OC(=O)-; A7 and A8 are each independently a bond; R1 and R2 are each independently C1-C 24 The hydrocarbon group is preferably C1-C 24 Alkyl, more preferably C3-C 12 Straight chain alkyl or C7-C 21 Branched alkyl groups, such as -C4H9, -C5H 11 、-C6H 13 、- C7H 15 、-C8H 17 、-C9H 19 、-CH(C4H9)2、-CH(C5H 11 )2、-CH(C6H 13 )2、-CH(C7H 15 )2、-CH(C8H 17 )2、-CH(C9H 19 )2、-CH2CH(C6H 13 )(C4H9).

[0817] In some embodiments, the amino lipid compound represented by formula (II-VIa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has the structure represented by formula (II-VIa-a):

[0818] in,

[0819] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9 and R2 are as defined in formula (II-VIa).

[0820] In some embodiments, the amino lipid compound represented by formula (II-VIa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIa-b):

[0821] in,

[0822] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9 and R 11 The definition of is as defined in formula (II-VIa).

[0823] In some embodiments, the amino lipid compound represented by formula (II-VIa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIa-c):

[0824] in,

[0825] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9 and R 11 The definition of is as defined in formula (II-VIa).

[0826] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0827] A1, A2, and A3 are one of the following:

[0828] (1) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, and A3 is C1-C5 alkylene or a bond;

[0829] (2) when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene or a bond, and A1 and A2 together with the nitrogen atom to which they are attached form a nitrogen-containing heterocyclic ring; or

[0830] (3) When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A3 is C1-C5 alkylene, and A1 and A3, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocycle;

[0831] (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene, and A1, A2 and A3, together with the nitrogen atom to which they are commonly attached, form a spirocyclic heterocycle, a fused heterocycle or a bridged heterocycle containing N;

[0832] A4 is a C1-C5 alkylene group or a bond;

[0833] A5, A6, A7 and A8 are each independently C1-C 18 Alkylidene, C1-C 18 heteroalkylene or bond;

[0834] Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-、-N(C(=O)A9SA 10 )-、-N(C(=O)A 11 )、-N(A9OA 10 )-、-N(A9SA 10 )-、-N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-;

[0835] R6 are each independently H or C1-C8 hydrocarbon group;

[0836] Each R9 and each R 11 Each independently C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl;

[0837] each A9 is a C1-C8 alkylene group or a bond;

[0838] Each A 10 and each A 11 Each is independently a C1-C8 hydrocarbon group;

[0839] Preferably, the hydrocarbon group is an alkyl group, an alkenyl group or an alkynyl group;

[0840] Preferably, the hydrocarbylene group is an alkylene group, an alkenylene group or an alkynylene group;

[0841] Preferably, the heteroalkyl group is a heteroalkyl group, a heteroalkenyl group or a heteroalkynyl group;

[0842] Preferably, the heteroalkylene group is a heteroalkylene group, a heteroalkenylene group or a heteroalkynylene group.

[0843] The amino lipid compound represented by formula (II-IVa), (II-VIa) or (II-VIa-c), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, when applicable, includes one or more of the following characteristics.

[0844] In some embodiments, A4 is a bond.

[0845] In some embodiments, Y1 is -Z3C(=O)Z4- or -N(R5)-.

[0846] In some embodiments, Y1 is -N(R6)C(=O)O-, -OC(=O)N(R6)-, or -OC(=O)O-.

[0847] In some embodiments, Y1 is -OC(=O)O-.

[0848] In some embodiments, Y1 is -N(R6)C(=O)O- or -OC(=O)N(R6)-.

[0849] In some embodiments, each R6 is independently H, or is replaced by -OC(=O)R 14 、-C(=O)OR 14 、-OR 14 Substituted C1-C8 alkyl.

[0850] In some embodiments, Y1 is -N(R6)C(=O)O- or -OC(=O)N(R6)-, wherein each R6 is independently -OC(=O)R 14 、-C(=O)OR 14 、-OR 14 Substituted C1-C8 alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl).

[0851] In some embodiments, Y1 is -N(H)C(=O)O-.

[0852] In some embodiments, Y1 is -OC(=O)N(H)-.

[0853] In some embodiments, Y1 is -N(R5)-.

[0854] In some embodiments, Y1 is -N(C(=O)A9OA 10 )-.

[0855] In some embodiments, Y1 is -N(C(=O)A 10 )-.

[0856] In some embodiments, Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -C(=O)S-, -SC(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, or -OP(=O)(H)O-.

[0857] In some embodiments, Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -N(H)C(=O)O-, or -OC(=O)N(H)-.

[0858] In some embodiments, Z1 and Z2 are each independently -C(=O)O- or -OC(=O)-.

[0859] In some embodiments, Z1 is -C(=O)O-.

[0860] In some embodiments, Z1 is -OC(=O)-.

[0861] In some embodiments, Z1 is -OC(=O)O-.

[0862] In some embodiments, Z1 is -N(H)C(=O)O-.

[0863] In some embodiments, Z1 is -OC(=O)N(H)-.

[0864] In some embodiments, Z2 is -C(=O)O-.

[0865] In some embodiments, Z2 is -OC(=O)-.

[0866] In some embodiments, Z2 is -OC(=O)O-.

[0867] In some embodiments, Z2 is -N(H)C(=O)O-.

[0868] In some embodiments, Z2 is -OC(=O)N(H)-.

[0869] In some embodiments, Z1 and Z2 are -C(=O)O-.

[0870] In some embodiments, Z1 and Z2 are -OC(=O)-.

[0871] In some embodiments, Z1 and Z2 are -OC(=O)O-.

[0872] In some embodiments, Z1 and Z2 are -N(H)C(=O)O-.

[0873] In some embodiments, Z1 and Z2 are -OC(=O)N(H)-.

[0874] In some embodiments, Z1 is -C(=O)O-, and Z2 is -OC(=O)-.

[0875] In some embodiments, A4 is a bond, and Z1 and Z2 are C(=O)O-.

[0876] In some embodiments, A4 is a bond, and Z1 and Z2 are -OC(=O)-.

[0877] In some embodiments, A4 is a bond, and Z1 and Z2 are -OC(=O)O-.

[0878] In some embodiments, A4 is a bond, and Z1 and Z2 are -N(H)C(=O)O-.

[0879] In some embodiments, A4 is a bond, and Z1 and Z2 are -OC(=O)N(H)-.

[0880] In some embodiments, A4 is a bond, Z1 is -C(=O)O-, and Z2 is -OC(=O)-.

[0881] In some embodiments, A 12 is C1-C3 alkylene, for example C2-C3 alkylene.

[0882] In some embodiments, A 12is a C1-C3 alkylene group (e.g., a C1 alkylene group), and A5 and A6 are each independently a C3-C9 alkylene group (e.g., a C4-C9 alkylene group, a C5-C9 alkylene group, a C6 alkylene group, a C7 alkylene group, a C8 alkylene group).

[0883] In some embodiments, R1 is -C(R6)(OR9)2.

[0884] In some embodiments, R1 is -C(H)(OR9)2.

[0885] In some embodiments, R2 is -C(R6)(OR 11 )2.

[0886] In some embodiments, R2 is -C(H)(OR 11 )2.

[0887] In some embodiments, R2 is Z7R 10 .

[0888] In some embodiments, R2 is -C(=O)OR 10 .

[0889] In some embodiments, R2 is -OC(=O)R 10 .

[0890] In some embodiments, R2 is -OR 10 .

[0891] In some embodiments, R2 is -N(H)C(=O)R 10 .

[0892] In some embodiments, R2 is -C(=O)N(R6)R 10 .

[0893] In some embodiments, R2 is substituted C1-C 24 Alkyl, such as substituted C5-C 16 Alkyl, substituted C6-C 14 Alkyl, substituted C6-C 12 In some embodiments, R2 is C1-C substituted with hydroxyl. 24 Alkyl, such as C5-C 16 Alkyl, such as C6-C substituted by hydroxy 14 Alkyl, C6-C substituted by hydroxy 12 Alkyl, C substituted by hydroxy 10 alkyl.

[0894] In some embodiments, R1 is -C(R6)(OR9)2, R2 is -C(R6)(OR 11 )2.

[0895] In some embodiments, R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

[0896] In some embodiments, R1 is -C(H)(OR9)2, R2 is -C(=O)OR 10 .

[0897] In some embodiments, R1 is -C(H)(OR9)2, R2 is -OC(=O)R 10 .

[0898] In some embodiments, R1 is -C(H)(OR9)2, R2 is -OR 10 .

[0899] In some embodiments, R1 is -C(H)(OR9)2, R2 is C1-C 24 Alkyl (e.g. R2 is C5-C 16 Alkyl, C6-C substituted by hydroxyl 14 Alkyl, C6-C substituted by hydroxyl 12 Alkyl or hydroxy-substituted C 10 alkyl).

[0900] In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -C(=O)OR 10 .

[0901] In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -OC(=O)R 10 .

[0902] In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -OR 10 .

[0903] In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is a substituted C1-C 24 Alkyl (e.g. R2 is substituted C5-C 16 Alkyl, substituted C6-C 14 Alkyl, substituted C6-C 12 Alkyl or substituted C 10 alkyl).

[0904] In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is C1-C 24 Alkyl (e.g. R2 is C5-C 16 Alkyl, C6-C substituted by hydroxyl 14 Alkyl, C6-C substituted by hydroxyl 12 Alkyl or hydroxy-substituted C 10 alkyl).

[0905] In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is C1-C 24 Alkyl (e.g. R2 is C5-C 16 Alkyl, C6-C substituted by hydroxyl 14 Alkyl, C6-C substituted by hydroxyl 12 Alkyl or hydroxy-substituted C 10 alkyl), A5 and A6 are each independently C2-C 10 Alkylene (e.g., C5-C9 alkylene, C8 alkylene).

[0906] In some embodiments, Y1 is -OC(=O)O-, A7 and A8 are unsubstituted C1-C5 alkylene (e.g., unsubstituted C2-C4 alkylene), R1 is -C(H)(OR9)2, and R2 is -C(=O)OR 10 .

[0907] In some embodiments, Y1 is -OC(=O)O-, A7 and A8 are unsubstituted C1-C5 alkylene (e.g., unsubstituted C2-C4 alkylene), R1 is -C(H)(OR9)2, R2 is -OC(=O)R 10 .

[0908] In some embodiments, Y1 is -N(H)C(=O)O-, R1 is -C(H)(OR9)2, and R2 is -C(H)(OR 11 )2.

[0909] In some embodiments, Y1 is -OC(=O)N(H)-, R1 is -C(H)(OR9)2, and R2 is -C(H)(OR 11 )2.

[0910] In some embodiments, Y1 is -N(C(=O)A9OA 10 )-, R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

[0911] In some embodiments, Y1 is -N(C(=O)A 10 )-, R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

[0912] In some embodiments, Y1 is -N(C(=O)A 10 )-, R1 is -C(H)(OR9)2, R2 is C1-C substituted by hydroxyl 24 Alkyl (e.g. R2 is C5-C 16 Alkyl, C6-C substituted by hydroxyl 14 Alkyl, C6-C substituted by hydroxyl 12 Alkyl or hydroxy-substituted C 10 alkyl).

[0913] In some embodiments, A9 is C1-C8 alkylene.

[0914] In some embodiments, A9 is C1-C5 alkylene.

[0915] In some embodiments, A9 is C1-C3 alkylene.

[0916] In some embodiments, A 10 It is a C1-C8 alkyl group, such as a C1, C2, C3, C5, or C8 alkyl group.

[0917] In some embodiments, R 10 C1-C 24 Alkyl, C2-C 24 Alkenyl or C2-C 24 Alkynyl.

[0918] In some embodiments, R 10 For straight chain C2-C 10 alkyl.

[0919] In some embodiments, R 10 It is a straight-chain C2-C8 alkyl group.

[0920] In some embodiments, R 10 For branched C7-C 18 Alkyl groups, such as:

[0921] In some embodiments, R 10 C5-C 16 Alkenyl.

[0922] In some embodiments, R 10 C5-C 12 Alkenyl.

[0923] In some embodiments, R 10 It is a C5-C8 alkenyl group, such as a C5 or C6 alkenyl group.

[0924] In some embodiments, R 10 C5-C 16 Alkynyl.

[0925] In some embodiments, R 10 C5-C 12 Alkynyl, such as C 10 Alkynyl.

[0926] In some embodiments, R9 is C9-C 11 Alkynyl, such as C 10 Alkynyl.

[0927] In some embodiments, R 14 C1-C 12 alkyl.

[0928] In some embodiments, R 14 It is a C1-C5 alkyl group.

[0929] In some embodiments, R 14 is a C2-C 12 Alkenyl.

[0930] In some embodiments, R 14 It is a C4-C8 alkenyl group having one double bond, for example, a C6 alkenyl group having one double bond.

[0931] In some embodiments, A5 and A6 are each independently C1-C 11 Alkylene.

[0932] In some embodiments, A5 and A6 are each independently C3-C 10 Alkylene.

[0933] In some embodiments, A5 and A6 are each independently C4-C9 alkylene.

[0934] In some embodiments, A5 and A6 are each independently C5-C9 alkylene, such as C6, C7, C8 alkylene.

[0935] In some embodiments, A7 and A8 are each independently C1-C 12 Alkylene.

[0936] In some embodiments, A7 and A8 are each independently C5-C 10 Alkylene.

[0937] In some embodiments, A7 and A8 are each independently C1-C5 alkylene.

[0938] In some embodiments, A7 and A8 are each independently C2-C4 alkylene.

[0939] In some embodiments, A7 and A8 are C3 alkylene.

[0940] In some embodiments, A7 or A8 is a bond.

[0941] In some embodiments, A7 is a bond.

[0942] In some embodiments, A8 is a bond.

[0943] In some embodiments, each R9 is independently C1-C 12 Alkyl, C5-C 16 Alkenyl or C5-C 16 Alkynyl.

[0944] In some embodiments, each R9 is independently C3-C9 alkyl.

[0945] In some embodiments, each R9 is independently C5-C8 alkyl, such as C6, C 7、 C8 alkyl.

[0946] In some embodiments, each R9 is independently C5-C 12 Alkenyl.

[0947] In some embodiments, each R9 is independently C5-C8 alkenyl, such as C6 alkenyl.

[0948] In some embodiments, each R9 is independently C9-C 11 Alkynyl, such as C 10 Alkynyl.

[0949] In some embodiments, each R 11 Each independently is C1-C 12 alkyl.

[0950] In some embodiments, each R 11 Each is independently a C3-C9 alkyl group.

[0951] In some embodiments, each R 11 Each independently is a C5-C8 alkyl group, such as C6, C 7、 C8 alkyl.

[0952] In some embodiments, each R 11 Each independently is C5-C12 Alkenyl.

[0953] In some embodiments, each R 11 Each is independently a C5-C8 alkenyl group, for example a C6 alkenyl group.

[0954] In some embodiments, each R 11 Each independently is C9-C 11 Alkynyl, such as C 10 Alkynyl.

[0955] In some embodiments, the dashed line connecting Al and A2 and the dashed line connecting Al and A3 are absent.

[0956] In some embodiments, the dashed line connecting Al and A2 is a bond and the dashed line connecting Al and A3 is not present.

[0957] In some embodiments, the dashed line connecting Al and A3 is a bond and the dashed line connecting Al and A2 is not present.

[0958] In some embodiments, A1 and A2 are each independently C1-C5 alkyl, or C1-C5 alkylene.

[0959] In some embodiments, A1 and A2 are each independently C1-C3 alkyl.

[0960] In some embodiments, A1 and A2 are each independently C1-C2 alkyl.

[0961] In some embodiments, A2 is C1-C3 alkyl, for example C1-C2 alkyl.

[0962] In some embodiments, A3 is C1-C5 alkylene.

[0963] In some embodiments, A3 is C2-C4 alkylene, such as C3 alkylene.

[0964] In some embodiments, the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, and A1 and A2 are each independently C1-C3 alkyl, for example, C1-C2 alkyl.

[0965] In some embodiments, the dotted line connecting A1 and A2 and the dotted line connecting A1 and A3 are absent, and A1 and / or A2 are unsubstituted C1-C5 alkyl, for example, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, or unsubstituted C1-C2 alkyl.

[0966] In some embodiments, the dotted line connecting A1 and A2 and the dotted line connecting A1 and A3 are absent, and A1 and A2 are each independently an unsubstituted C1-C5 alkyl group, for example, an unsubstituted C1-C4 alkyl group, an unsubstituted C1-C3 alkyl group, or an unsubstituted C1-C2 alkyl group.

[0967] In some embodiments, the dotted line connecting A1 and A2 and the dotted line connecting A1 and A3 are absent, and A1 and / or A2 are substituted C1-C5 alkyl, for example, substituted C1-C4 alkyl, substituted C1-C3 alkyl, or substituted C1-C2 alkyl.

[0968] In some embodiments, when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 and / or A2 is C1-C5 alkylene.

[0969] In some embodiments, when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 and A2 together with the nitrogen atom to which they are commonly attached form a four-membered, five-membered, or six-membered N-containing heterocyclic ring.

[0970] In some embodiments, when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 and / or A2 is unsubstituted C1-C5 alkylene.

[0971] In some embodiments, when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 and A2 are each independently unsubstituted C1-C5 alkylene.

[0972] In some embodiments, when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 and / or A2 is a substituted C1-C5 alkylene.

[0973] In some embodiments, when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A2 is C1-C3 alkyl, and A1 and / or A3 is C1-C5 alkylene.

[0974] In some embodiments, when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 and A3 together with the nitrogen atom to which they are commonly attached form a four-membered, five-membered, or six-membered N-containing heterocyclic ring.

[0975] In some embodiments, when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is unsubstituted C1-C5 alkylene and A2 is unsubstituted C1-C5 alkyl (e.g., unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, unsubstituted C1-C2 alkyl).

[0976] In some embodiments, when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is unsubstituted C1-C5 alkylene and A2 is substituted C1-C5 alkyl (e.g., substituted C1-C4 alkyl, substituted C1-C3 alkyl, substituted C1-C2 alkyl).

[0977] In some embodiments, when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is a substituted C1-C5 alkylene and A2 is an unsubstituted C1-C5 alkyl (e.g., an unsubstituted C1-C4 alkyl, an unsubstituted C1-C3 alkyl, an unsubstituted C1-C2 alkyl).

[0978] In some embodiments, when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is a substituted C1-C5 alkylene and A2 is a substituted C1-C5 alkyl (e.g., a substituted C1-C4 alkyl, a substituted C1-C3 alkyl, a substituted C1-C2 alkyl).

[0979] In some embodiments, A1 or A2 is hydroxy, -OR 12 、-C(=O)OR 12 、-OC(=O)R 12 or C1-C5 alkyl, C1-C2 alkyl or C1-C5 alkylene substituted by C1-C5 alkyl, wherein R 12 Each independently C1-C 12 Alkyl, for example, A1 or A2 is

[0980] In some embodiments, A1 and A2 are each independently a C1-C5 alkyl group, a C1-C2 alkyl group, or a C1-C5 alkylene group substituted with a C1-C3 alkyl group, for example: In some embodiments, A3 is unsubstituted C1-C5 alkylene.

[0981] In some embodiments, A3 is unsubstituted C2-C4 alkylene.

[0982] In some embodiments, A3 is unsubstituted C3 alkylene.

[0983] In some embodiments, A3 is substituted C1-C5 alkylene, such as substituted C2-C4 alkylene, substituted C3 alkylene.

[0984] In some embodiments, A3 is replaced by one or two R 14 Substituted C3 alkylene, wherein R 14 C1-C 12 Alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl, C1 alkyl).

[0985] In some embodiments, A3 is separated by two -R 14 Substituted C3 alkylene, wherein R 14 C1-C 12 Alkyl (e.g. C1-C5 alkyl, C1-C3 alkyl, C1 alkyl). For example, A3 is

[0986] In some embodiments, Has one of the following structures:

[0987] Wherein, c is 1, 2, 3, 4 or 5.

[0988] In some embodiments, each R9 and / or each R 11 For the -R 13 OC(=O)R 14 、-R 13 C(=O)OR 14 or -R 13 OR 14 Substituted C1-C 12 Alkyl (e.g., C3-C9 alkyl, C5-C8 alkyl, C6 alkyl), wherein R 14 C1-C 12 Alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl, C1 alkyl).

[0989] In some embodiments, R9 and R 11 For the -R 13 OC(=O)R 14 、-R 13 C(=O)OR 14 or -R 13 OR 14 Substituted C2-C5 alkyl (e.g., C3-C4 alkyl), wherein R 14 C1-C 12 Alkyl (e.g. C1-C5 alkyl, C1-C3 alkyl, C1 alkyl). For example: R9 and R 11 for

[0990] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0991] Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-, A4 is a bond, A5 and A6 are each independently C3-C 10 Alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is each independently C3-C9 alkyl, each R 11 Each is independently a C3-C9 alkyl group, the dotted line connecting A1 and A2 and the dotted line connecting A1 and A3 do not exist, A1 and A2 are each independently a C1-C3 alkyl group, and A3 is a C2-C4 alkylene group.

[0992] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein Z1 and Z2 are -C(=O)O-, A4 is a bond, and A5 and A6 are each independently C3-C 10 Alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is each independently C3-C9 alkyl, each R 11 Each is independently a C3-C9 alkyl group, the dotted line connecting A1 and A2 and the dotted line connecting A1 and A3 do not exist, A1 and A2 are each independently a C1-C3 alkyl group, and A3 is a C2-C4 alkylene group.

[0993] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-, A4 is a bond, A5 and A6 are each independently C3-C 10 Alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is each independently C3-C9 alkyl, each R 11 Each is independently a C3-C9 alkyl group, the dotted line connecting A1 and A2 is a bond and the dotted line connecting A1 and A3 does not exist, A1 and A2 are each independently a C1-C5 alkylene group, and A3 is a C2-C4 alkylene group.

[0994] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-, A4 is a bond, A5 and A6 are each independently C3-C 10Alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is each independently C3-C9 alkyl, each R 11 Each is independently a C3-C9 alkyl group, the dotted line connecting A1 and A2 is a bond and the dotted line connecting A1 and A3 does not exist, A1 and A2 together with the nitrogen atom to which they are commonly connected form a four-membered, five-membered or six-membered heterocycle containing N, and A3 is a C2-C4 alkylene group.

[0995] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-, A4 is a bond, A5 and A6 are each independently C3-C 10 Alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is each independently C3-C9 alkyl, each R 11 A1 and A3 are each independently C3-C9 alkyl, the dotted line connecting A1 and A3 is a bond and the dotted line connecting A1 and A2 does not exist, A2 is C1-C3 alkyl, and A1 and A3 are each independently C1-C5 alkylene.

[0996] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-, A4 is a bond, A5 and A6 are each independently C3-C 10 Alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is each independently C3-C9 alkyl, each R 11 Each is independently a C3-C9 alkyl group, the dotted line connecting A1 and A3 is a bond and the dotted line connecting A1 and A2 does not exist, A2 is a C1-C3 alkyl group, and A1 and A3 together with the nitrogen atom to which they are commonly attached form a four-membered, five-membered or six-membered heterocyclic ring containing N.

[0997] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has formula (II-VIb):

[0998] in,

[0999] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1 and R2 are as defined in formula (II-I).

[1000] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond.

[1001] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkylene.

[1002] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Hydrocarbylene.

[1003] In some embodiments, A5 and A6 are each independently C 11 、C 12 、C 13 or C 14 Hydrocarbylene.

[1004] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C 17 or C 18 Hydrocarbylene.

[1005] In some embodiments, A5 and A6 are each independently C1, C2 alkylene or a bond.

[1006] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkylene.

[1007] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Alkylene.

[1008] In some embodiments, A5 and A6 are each independently C 11 、C 12 、C 13 or C 14 Alkylene.

[1009] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C 17 or C 18 Alkylene.

[1010] In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond.

[1011] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkenylene.

[1012] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Alkenylene.

[1013] In some embodiments, A5 and A6 are each independently C 11 、C12 、C 13 or C 14 Alkenylene.

[1014] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C 17 or C 18 Alkenylene.

[1015] In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond.

[1016] In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkynylene.

[1017] In some embodiments, A5 and A6 are each independently C7, C8, C9 or C 10 Alkynylidene.

[1018] In some embodiments, A5 and A6 are each independently C 11 、C 12 、C 13 or C 14 Alkynylidene.

[1019] In some embodiments, A5 and A6 are each independently C 15 、C 16 、C 17 or C 18 Alkynylidene.

[1020] In some embodiments, the amino lipid compound represented by formula (II-VIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIb-a):

[1021] in,

[1022] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9 and R2 are as defined in formula (II-VIb).

[1023] In some embodiments, the amino lipid compound represented by formula (II-VIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIb-b):

[1024] in,

[1025] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9 and R 11The definition of is as defined in formula (II-VIb).

[1026] In some embodiments, the amino lipid compound represented by formula (II-VIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIb-c):

[1027] in,

[1028] A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9 and R 11 The definition of is as defined in formula (II-VIb).

[1029] In some embodiments, the present disclosure provides formula (II-I), (II-Ia), (II-Ib), (II-Ic), (II-Id), (II-Ie), (II-II), (II-IIa), (II-IIb), (II-III), (II-IIIa), (II-IIIb), (II-IVa), (II-IVb), (II-Va), (II-Vb), (II-Vc), (II-Vd), (II-Ve), (II-Vf), (II-Vg), (II-Vh), (II-VIa), (II-VIa-a), (II-VIa-b), (II-VIa-c) (II-VIb), (II-VIb-a), (II-VIb-b) or (II-VIb-c), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the alkyl, alkylene, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, heteroalkyl or heteroalkylene is optionally substituted with hydroxy, ester, alkoxy, alkyl, halogen, oxygen, sulfur, amino, amide.

[1030] In some embodiments, the present disclosure provides an amino lipid compound of Formula (II-I), (II-Ia), (II-Ib), (II-Ic), (II-Id), (II-Ie), (II-II), (II-IIa), (II-IIb), (II-III), (II-IIIa), (II-IIIb), (II-IVa), (II-IVb), (II-Va), (II-Vb), (II-Vc), (II-Vd), (II-Ve), (II-Vf), (II-Vg), (II-Vh), (II-VIa), (II-VIa-a), (II-VIa-b), (II-VIa-c) (II-VIb), (II-VIb-a), (II-VIb-b) or (II-VIb-c) as described above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound has one of the structures shown in Table 1 below.

[1031] Table 1

[1032] The amino lipid compounds of the present disclosure all have hydrophobic characteristics due to the presence of long non-polar residues, and simultaneously have hydrophilic characteristics due to the amino group. Due to this amphipathic characteristic, the amino lipid compounds of the present disclosure can be used to form lipid nanoparticles, such as lipid bilayers, micelles, liposomes, etc. Within the scope of the present disclosure, the term "lipid nanoparticle" means a nanometer-sized material obtained by placing an amino lipid compound in an aqueous solution. These particles are particularly lipid nanoparticles, lipid bilayer vesicles (liposomes), multilamellar vesicles or micelles.

[1033] In some embodiments, the lipid nanoparticle is a liposome containing an amino lipid compound of the present disclosure.In the scope of the present disclosure, a liposome is a microvesicle composed of a bilayer of lipid amphiphilic molecules enclosing an aqueous compartment.

[1034] Liposome formation is not a spontaneous process. Lipid vesicles first form when lipids are placed in water, forming a bilayer or a series of bilayers, each separated by water molecules. Liposomes can be formed by treating lipid vesicles in water with ultrasound.

[1035] For the purposes of this disclosure, the term "lipid bilayer" refers to a thin membrane 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 solutions form aggregates upon contact with water, with the hydrophilic head regions sequestering the hydrophobic single tail region at the center of the micelle.

[1036] In one aspect, the present disclosure provides a use of the amino lipid compound of the present disclosure for preparing a delivery vehicle for an active ingredient. In some embodiments, the delivery vehicle is in the form of a lipid nanoparticle, such as a lipid bilayer, micelle, or liposome.

[1037] Lipid nanoparticles (LNPs)

[1038] In another aspect, the present disclosure provides lipid nanoparticles containing the amino lipid compounds of the present disclosure.

[1039] In some embodiments, the lipid nanoparticles further contain one or more of a helper lipid, a structural lipid, and a PEG-lipid (polyethylene glycol-lipid).

[1040] In some further embodiments, the lipid nanoparticle further contains the helper lipid, the structural lipid, and the PEG-lipid.

[1041] In some embodiments, the lipid nanoparticles comprise the following amount (molar percentage) of the amino lipid compound, based on the total amount of the amino lipid compound, the helper lipid, the structural lipid and the PEG-lipid: about 25.0%-75.0%, for example, 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%.

[1042] In some embodiments, the lipid nanoparticles comprise the helper lipid in the following amount (molar percentage), based on the total amount of the amino lipid compound, the helper lipid, the structural lipid, and the PEG-lipid: about 5.0%-45.0%, for example, 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%.

[1043] In some embodiments, the lipid nanoparticles comprise the following amount (molar percentage) of the structural lipid, based on the total amount of the amino lipid compound, the helper lipid, the structural lipid, and the PEG-lipid: about 0.0%-50.0%, for example, 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%-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%.

[1044] In some embodiments, the lipid nanoparticles comprise the following amount (molar percentage) of the PEG-lipid, based on the total amount of the amino lipid compound, the helper lipid, the structural lipid, and the PEG-lipid: about 0.5%-5.0%, for example, 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%.

[1045] In some embodiments as described above, the helper lipid is a phospholipid. The phospholipid is generally semi-synthetic, but may also be of natural origin or chemically modified. The phospholipid includes, but is not limited to, DSPC (distearoylphosphatidylcholine), DOPE (dioleoylphosphatidylethanolamine), DOPC (dioleoylphosphatidylcholine), DOPS (dioleoylphosphatidylserine), DSPG (1,2-dioctadecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol)), DPPG (dipalmitoylphosphatidylglycerol), DPPC (dipalmitoylphosphatidylcholine), DGTS (1,2-dipalmitoyl-sn-glycero-3-O-4'-(N,N,N-trimethyl)homoserine), lysophospholipids, and the like. Preferably, the helper lipid is one or more selected from DSPC, DOPE, DOPC, and DOPS. In some embodiments, the helper lipid is DSPC and / or DOPE.

[1046] In some embodiments, the structured lipid is a sterol substance, including but not limited to cholesterol, cholesterol ester, sterol hormones, sterol vitamins, bile acid, cholesterol, ergosterol, β-sitosterol and oxidized cholesterol derivatives. Preferably, the structured lipid is at least one selected from cholesterol, cholesterol ester, sterol hormones, sterol vitamins and bile acids. In some embodiments, the structured lipid is cholesterol, preferably high-purity cholesterol, especially injection-grade high-purity cholesterol, such as CHO-HP (produced by AVT).

[1047] As used herein, the term PEG-lipid (polyethylene glycol-lipid) is a conjugate of polyethylene glycol and a lipid structure. Preferably, the PEG-lipid is selected from PEG-DMG and PEG-distearoylphosphatidylethanolamine (PEG-DSPE), preferably PEG-DMG. Preferably, the PEG-DMG is a polyethylene glycol (PEG) derivative of 1,2-dimyristyl glycerol. Preferably, the average molecular weight of the PEG is about 2000 to 5000, preferably about 2000.

[1048] In some embodiments as described above, in the lipid nanoparticles, the molar ratio of the amino lipid compound of the present disclosure: helper lipid: structural lipid: PEG-lipid is 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: :39.5:2.5, 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 45.0:15.0:3 8.5:1.5, 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.

[1049] In other embodiments as described above, in the lipid nanoparticles, the molar ratio of the amino lipid compound of the present disclosure: helper lipid: structural lipid: PEG-lipid is 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 50.0:15.0:33.5:1.5, 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.

[1050] In some embodiments, the lipid nanoparticles have the amino lipid compound, helper lipid, structural lipid and PEG-lipid of the present disclosure in the mole percentages (%) shown in No. 1-24 in Table 2 below, based on the total amount of the amino lipid compound, the helper lipid, the structural lipid and the PEG-lipid:

[1051] Table 2

[1052] In some embodiments, the lipid nanoparticles have the amino lipid compound, helper lipid, structural lipid and PEG-lipid of the present disclosure in the mole percentages (%) shown in No. 25-42 in Table 3 below, based on the total amount of the amino lipid compound, the helper lipid, the structural lipid and the PEG-lipid:

[1053] Table 3

[1054] As described above, the lipid nanoparticles of the present disclosure can be used as delivery vehicles for active ingredients.

[1055] In some embodiments, the active ingredient comprises a therapeutic and / or prophylactic agent.

[1056] The term "therapeutic agent" or "prophylactic agent" refers to any agent that, when administered to a subject, has a therapeutic, diagnostic, and / or prophylactic effect and / or elicits a desired biological and / or pharmacological effect.

[1057] An "effective amount" or "therapeutically effective amount" refers to an amount of a compound of the invention, or a lipid nanoparticle comprising the compound of the invention, sufficient to achieve treatment in a mammal (preferably a human) when administered to the mammal (preferably a human). The amount of lipid nanoparticles of the invention that constitutes a "therapeutically effective amount" will depend on the compound, the condition and its severity, the mode of administration, and the age of the mammal to be treated, but can be routinely determined by one of ordinary skill in the art based on their own knowledge and this disclosure.

[1058] Preferably, the pharmaceutical active ingredient is a bioactive ingredient, which is a substance that has a biological effect when introduced into a cell or host, for example, by stimulating an immune response or an inflammatory response, by exerting enzymatic activity, or by complementing a mutation. Bioactive ingredients include, but are not limited to, nucleic acids, proteins, peptides, antibodies, small molecules, and mixtures thereof.

[1059] Preferably, the biologically active component is a nucleic acid.

[1060] In some embodiments, the bioactive ingredient is an anti-tumor agent, an antibiotic, an immunomodulator, an anti-inflammatory agent, an agent acting on the central nervous system, a polypeptide, a polypeptoid, or a mixture thereof.

[1061] When lipid nanoparticles encapsulate active ingredients in their internal aqueous space, they can be referred to as "lipid nanoparticle drugs."

[1062] In the context of the present disclosure, the term "cell" is a general term and includes cultures of single cells, tissues, organs, insect cells, avian cells, fish cells, amphibian cells, mammalian cells, primary cells, continuous cell lines, stem cells, and / or genetically engineered cells (e.g., recombinant cells expressing heterologous polypeptides or proteins). Recombinant cells include, for example, cells expressing heterologous polypeptides or proteins (e.g., growth factors or blood factors).

[1063] In some embodiments as described above, the lipid nanoparticles of the present disclosure further contain a nucleic acid.

[1064] In some embodiments, in the lipid nanoparticles, the mass ratio of the amino lipid compound of the present disclosure to the nucleic acid is about (5-30):1, such as about (5-10):1, (10-15):1, (15-20):1, (20-25):1 or (25-30):1, preferably about 10:1.

[1065] In some embodiments, the nucleic acid is selected from RNA, antisense oligonucleotide, DNA.

[1066] In some embodiments, the RNA is selected from messenger RNA (mRNA), ribosomal RNA (rRNA), microRNA (miRNA), transfer RNA (tRNA), small inhibitory RNA (siRNA), small nuclear RNA (snRNA), small hairpin RNA (shRNA), single-stranded guide RNA (sgRNA), cas9 mRNA, or a mixture thereof.

[1067] In some embodiments, the messenger RNA (mRNA) encodes a polypeptide and / or protein of interest. This includes any naturally occurring or non-naturally occurring or otherwise modified polypeptide. In some embodiments, the polypeptide and / or protein encoded by the mRNA can have a therapeutic and / or preventive effect when expressed in a cell.

[1068] In some embodiments, the RNA is a siRNA that can selectively reduce the expression of a gene of interest or downregulate the expression of the gene. For example, the selection of the siRNA can silence the gene associated with a particular disease, disorder, or condition after the lipid nanoparticles comprising the siRNA are administered to a subject in need. The siRNA can comprise a sequence complementary to the mRNA sequence encoding a gene or protein of interest. In some embodiments, the siRNA can be an immunomodulatory siRNA.

[1069] In certain embodiments, the RNA is sgRNA and / or cas9 mRNA. sgRNA and / or cas9 mRNA can be used as gene editing tools. For example, the sgRNA-cas9 complex can affect the translation of mRNA of a cellular gene.

[1070] In some embodiments, the RNA is shRNA or its encoding vector or plasmid. shRNA can be produced inside the target cell after the appropriate construct is delivered to the nucleus. The construct and mechanism associated with shRNA are well known in the relevant art.

[1071] In some embodiments, the DNA is a plasmid.

[1072] In some embodiments, the lipid nanoparticles are used to transfer nucleic acids. In some embodiments, the lipid nanoparticles can be used, for example, for gene therapy, genetic vaccination, protein replacement therapy, antisense therapy, or therapy performed by interfering RNA.

[1073] Pharmaceutical composition

[1074] In another aspect, the present invention provides a pharmaceutical composition comprising the lipid nanoparticles as described above and a pharmaceutically acceptable carrier, diluent or excipient.

[1075] In some embodiments, the pharmaceutical composition further comprises a buffer. In some such embodiments, the buffer is selected from phosphate buffer and Tris buffer, preferably phosphate buffer. In some embodiments, the concentration of the buffer is about 5 mmol / L-30 mmol / L, preferably about 10 mmol / L. In some embodiments, the pH of the buffer is about 6-8, preferably about 7-8, and more preferably about 7-7.5.

[1076] In some embodiments, the pharmaceutical composition further comprises a cryoprotectant. In some such embodiments, the cryoprotectant is selected from sucrose and trehalose, preferably sucrose. In some embodiments, the concentration of the cryoprotectant is about 50 mg / ml-100 mg / ml.

[1077] In some embodiments as 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 concentration of the cryoprotectant is about 50 mg / ml-100 mg / ml.

[1078] use

[1079] The lipid nanoparticles of the present disclosure have excellent performance in encapsulating bioactive ingredients. Lipid nanoparticles containing bioactive ingredients can be used to deliver any of a variety of therapeutic agents into cells. The present disclosure includes the use of lipid nanoparticles as described above to deliver bioactive ingredients into cells. The present invention also provides methods for delivering bioactive ingredients into cells, tissues, or organs, comprising contacting lipid nanoparticles of the present disclosure containing the bioactive ingredients with the cells, tissues, or organs. This provides new therapeutic treatment possibilities for individuals.

[1080] In some embodiments, the tissue or organ is selected from the group consisting of spleen, liver, kidney, lung, femur, eye tissue, vascular endothelium in blood vessels, lymphatic, and tumor tissue.

[1081] Preferably, the cell is a mammalian cell; further preferably, the mammalian cell is in a mammal. As used herein, a subject can be any mammal, preferably selected from mice, rats, pigs, cats, dogs, horses, goats, cows, and monkeys. In some preferred embodiments, the subject is a human.

[1082] The present disclosure provides a method for producing a polypeptide and / or protein of interest in a mammalian cell, the method comprising contacting the cell with a lipid nanoparticle comprising mRNA encoding the polypeptide and / or protein of interest, wherein after the cell contacts the lipid nanoparticle, the mRNA can be absorbed into the cell and translated to produce the polypeptide and / or protein of interest.

[1083] In another aspect, the present disclosure provides use of the amino lipid compound, lipid nanoparticle, or pharmaceutical composition of the present disclosure in the preparation of a drug. Preferably, the drug is a nucleic acid drug. Preferably, the pharmaceutical composition is used for the treatment and / or prevention of a disease.

[1084] In some embodiments, the disease is selected from the group consisting of rare diseases, infectious diseases, cancer, genetic diseases, autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases, and metabolic diseases.

[1085] Such medicaments are used, for example, in gene therapy, protein replacement therapy, antisense therapy or therapy by interfering RNA and genetic vaccination.

[1086] 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's disease.

[1087] In some embodiments, the genetic vaccination is preferably used to treat and / or prevent cancer, allergy, toxicity and pathogen infection. In some embodiments, the pathogen is selected from one or more of viruses, bacteria or fungi.

[1088] The present disclosure provides a method for treating a disease or condition in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the lipid nanoparticle according to the aforementioned method.

[1089] Preferably, the disease or condition is selected from the group consisting of rare diseases, infectious diseases, cancer, genetic diseases, autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases, and metabolic diseases.

[1090] In another aspect, the present disclosure provides the use of the amino lipid compound, lipid nanoparticle or pharmaceutical composition of the present disclosure in the preparation of a drug for nucleic acid transfer. In some embodiments, the nucleic acid is selected from RNA, antisense oligonucleotides, DNA. In some embodiments, the RNA is selected from emissive RNA (mRNA), ribosomal RNA (rRNA), microRNA (miRNA), transfer RNA (tRNA), small inhibitory RNA (siRNA), small nuclear RNA (snRNA), small hairpin RNA (shRNA), single-stranded guide RNA (sgRNA), cas9mRNA or a mixture thereof. In some embodiments, the DNA is a plasmid.

[1091] Preparation method

[1092] In another aspect, the present disclosure also provides a general synthetic method for preparing the amino lipid compound of formula (Id) or (Ie) of the present disclosure, as shown below:

[1093] In another aspect, the present disclosure also provides a general synthetic method for preparing the amino lipid compound of formula (II-I) of the present disclosure, as shown below:

[1094] (1) When X is C, Y1 is -Z3C(=O)Z4-, and Z3 and Z4 are not bonds, A 12 When is a key,

[1095] or

[1096] (2) When X is C and Y1 is -N(R5),

[1097] or

[1098] (3) When X is C, Y1 is -Z3C(=O)Z4, and Z3 is a bond and Z4 is not a bond,

[1099] or

[1100] (4) When X is C, Y1 is -Z3C(=O)Z4, and Z3 is not a bond, and Z4 is a bond,

[1101] or

[1102] (5) X is N, Y1 is -Z3C(=O)Z4-, and Z4 is a bond, A 12 When is a key,

[1103] or

[1104] (6) X is N, Y1 is -Z3C(=O)Z4-, and Z4 is a bond, A 12 When not a key,

[1105] In another aspect, the lipid nanoparticles or pharmaceutical compositions of the present invention can be prepared according to methods known in the art. For example, the method can include the following steps:

[1106] (1) Ingredients: preparing a suitable aqueous phase; and preparing an organic phase comprising the amino lipid compound of the present disclosure and optionally a helper lipid, a structural lipid and / or a PEG-lipid;

[1107] (2) Encapsulation: mixing appropriate amounts of the aqueous phase and the organic phase;

[1108] (3) Dialysis: Optionally, the mixture of step (2) is dialyzed;

[1109] (4) Sterilization: The product of step (3) is optionally sterilized, for example, by passing it through a sterilizing filter, such as a 0.22 μm microporous filter membrane.

[1110] In some embodiments, the lipid nanoparticles or pharmaceutical compositions of the present disclosure containing nucleic acids, particularly mRNA, can be prepared by a method comprising the following steps:

[1111] (1) Ingredients: preparing an aqueous phase containing the nucleic acid; and preparing an organic phase (e.g., an ethanol phase) containing the amino lipid compound of the present disclosure and optionally a helper lipid, a structural lipid, and / or a PEG-lipid;

[1112] (2) Encapsulation: mixing appropriate amounts of the aqueous phase and the organic phase;

[1113] (3) Dialysis: Optionally, the mixture of step (2) is dialyzed;

[1114] (4) Sterilization: The product of step (3) is optionally sterilized, for example, by passing it through a sterilizing filter, such as a 0.22 μm microporous filter membrane. Beneficial effects

[1115] The amino lipid compounds disclosed herein can form delivery vehicles with excellent bioactive ingredient encapsulation properties, such as lipid nanoparticles, which can be used for the delivery of bioactive ingredients, particularly poorly water-soluble drugs or active ingredients that are easily decomposed or degraded (e.g., nucleic acids), to improve their bioavailability and efficacy, or immunological activity, or transfection efficiency (for nucleic acids), or safety, or tissue and / or cell targeting or specificity, or preference for specific organs and / or tissues. BRIEF DESCRIPTION OF THE DRAWINGS

[1116] Figures 1 and 2 show the in vivo safety (ALT enzyme activity) test results of lipid nanoparticles containing different amino lipid compounds;

[1117] Figures 3 and 4 show the in vivo safety (AST enzyme activity) test results of lipid nanoparticles containing different amino lipid compounds;

[1118] FIG5 shows the in vivo delivery results of lipid nanoparticles containing different amino lipid compounds;

[1119] FIG6 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations in the spleen;

[1120] FIG7 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations of PBMCs.

[1121] In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention is described below in conjunction with specific embodiments. The following embodiments are only used to illustrate the present invention, rather than to limit it.

[1122] Example

[1123] The following examples are provided for purposes of illustration and not limitation.

[1124] Experimental methods without specific conditions specified in the examples are generally conventional conditions, or conditions recommended by the raw material or product manufacturers; reagents without source specified are generally conventional reagents available through commercial channels.

[1125] The abbreviations used in the examples have the following meanings:

[1126] Pd / C palladium / carbon;

[1127] EA ethyl acetate;

[1128] DCM dichloromethane;

[1129] TEA triethylamine;

[1130] MPa megapascals;

[1131] DMF N,N-dimethylformamide;

[1132] EDCI 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride;

[1133] DMAP 4-dimethylaminopyridine;

[1134] TBAF Tetrabutylammonium fluoride

[1135] TEMPO 2,2,6,6-tetramethylpiperidinyl N-oxide;

[1136] NaDCC sodium dichloroisocyanurate;

[1137] TBSCl tert-butyldimethylsilyl chloride;

[1138] h hour;

[1139] min points.

[1140] Example 1 Synthesis of amino lipid compound 383

[1141] Step 1: Synthesis of DFSGN-T

[1142] Reaction formula:

[1143] Experimental process:

[1144] To a 100 mL round-bottom flask, EDCI (4.43 g, 23.13 mmol), DCM (26 mL), and TEA (2.34 g, 23.13 mmol) were added sequentially. The mixture was shaken and stirred for 5 minutes, followed by the addition of DMAP (0.47 g, 3.86 mmol), BHB (4,4-bis(heptyloxy)butanol) (4.2 g, 13.88 mmol), and DTN (10-oxononadecanedioic acid) (2.64 g, 7.71 mmol). The mixture was stirred at room temperature overnight. After the reaction, DCM (100 mL) and water (150 mL) were added, and the mixture was extracted with stirring. The layers were separated, and the organic phase was collected and washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 7.7 g of crude DFSGN-T. The crude product was eluted with ethyl acetate:n-heptane = 1.5:1 to obtain 5.13 g of DFSGN-T, an 81% yield.

[1145] Step 2: Synthesis of DFSGN-C

[1146] Experimental process:

[1147] To a 250 mL single-necked flask, DFSGN-T (5.13 g, 5.62 mmol) was added, dissolved in methanol (50 mL), and cooled to 0°C. Sodium borohydride (0.23 g, 6.18 mmol) was added portionwise with stirring, and the mixture was incubated for 1 h. After the reaction was complete, the solvent was evaporated under reduced pressure, and water (100 mL) and DCM (100 mL) were added. The mixture was stirred and extracted. The organic phase was separated and collected, washed with water (50 mL), and concentrated under reduced pressure at 45°C to obtain 5.2 g of crude DFSGN-C. The crude product was eluted with ethyl acetate:n-heptane = 1.5:1 to obtain 4.5 g of DFSGN-C, with a yield of 88%.

[1148] Step 3: Synthesis of 383-D

[1149] Reaction formula:

[1150] Experimental process:

[1151] To a 50 mL single-necked round-bottom flask were added DFSGN-C (1.8 g, 1.97 mmol), DCM (18 mL), DMAP (72 mg, 0.60 mmol), and pyridine (0.39 g, 4.93 mmol). The mixture was stirred at room temperature, and p-nitrophenyl chloroformate (0.79 g, 3.94 mmol) was added portionwise. Stirring was continued for 1 h. Upon completion of the reaction, the mixture was diluted with water (150 mL) and extracted with DCM (100 mL). The organic phase was collected, washed with water (80 mL), and concentrated under reduced pressure to afford 3.0 g of crude 383-D. This crude product was eluted with ethyl acetate:n-heptane (1.5:1) to afford 1.74 g of 383-D, a yield of 82%.

[1152] Step 4: Synthesis of amino lipid compound 383

[1153] Reaction formula:

[1154] Experimental process:

[1155] To a 50 mL single-necked round-bottom flask were added 383-D (1.74 g, 1.61 mmol), DCM (18 mL), DMAP (59 mg, 0.48 mmol), triethylamine (0.49 mg, 4.84 mmol), and diethylaminopropanol (1.27 g, 9.68 mmol) and stirred at room temperature for 2 days. After the reaction was completed, the mixture was diluted with water (100 mL) and extracted with DCM (100 mL). The organic phase was collected, washed with water (80 mL), and concentrated under reduced pressure to obtain 2.8 g of crude amino lipid compound 383. The crude product was eluted with ethyl acetate:n-heptane = 1.5:1 to obtain 945 mg of amino lipid compound 383, a yield of 55% and a purity of 96.55%.

[1156] Amino lipid compound 383

[1157] 1 H NMR in CDCl3δ4.69-4.65(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.6Hz,2H),4. 07(t,J=6.1Hz,4H),3.58-3.54(m,4H),3.42-3.38(m,4H),2.53-2.49(m,6H ),2.28(t,J=7.5Hz,4H),1.83-1.79(m,2H),1.71-1.66(m,12H),1.61-1.52 (m,12H),1.36-1.28(m,52H),1.01(t,J=7.2Hz,6H)0.88(t,J=7.1Hz,12H).

[1158] LC-MS(ESI):Calculated for(M+H)1070.92,Found 1071.5.

[1159] Example 2 Synthesis of amino lipid compound 382

[1160] According to the general synthetic method, compound BSB was substituted for BHB, and amino lipid compound 382 was prepared according to the method of Example 1 to obtain 655 mg of amino lipid compound 382 with a yield of 58% and a purity of 97.63%.

[1161] BSB

[1162] Amino lipid compound 382

[1163] 1 H NMR in CDCl3δ4.69-4.65(m,1H),4.48(t,J=5.1Hz,2H),4.17(t,J=6.5Hz,2H),4. 07(t,J=6.0Hz,4H),3.58-3.55(m,4H),3.42-3.38(m,4H),2.53-2.49(m,6H ),2.28(t,J=7.6Hz,4H),1.84-1.79(m,2H),1.74-1.65(m,12H),1.61-1.52 (m,12H),1.37-1.27(m,44H),1.01(t,J=7.2Hz,6H)0.89(t,J=6.9Hz,12H).

[1164] LC-MS(ESI):Calculated for(M+H)1014.85,Found 1015.4.

[1165] Example 3 Synthesis of amino lipid compound 1245

[1166] Step 1: Synthesis of 3-bromopropanal

[1167] Reaction formula:

[1168] Experimental process:

[1169] To a 500 mL single-necked flask, 3-bromopropanol (10.0 g, 72 mmol) and DCM (150 mL) were added, and TEMPO (225 mg, 1.44 mmol), potassium bicarbonate (5.05 g, 50.4 mmol), and sodium bromide (296 mg, 2.88 mmol) were added under stirring. The reaction solution was cooled to 5 ° C. and an aqueous solution of NaDCC (9.5 g, 43.2 mmol) was added dropwise. After the addition was complete, the reaction was carried out at 5 ° C. for 3 h, filtered, and the filter cake was washed once with 20 mL of water and 20 mL of DCM. The organic phase was collected and concentrated under reduced pressure to obtain crude 3-bromopropanal. The crude product was chromatographed on a silica gel column using DCM as the eluent to obtain 9.0 g of 3-bromopropanal with a yield of 91.2%.

[1170] Step 2: Synthesis of 3,3-dioctyloxypropane

[1171] Reaction formula:

[1172] Experimental process:

[1173] To a 250 mL single-necked flask, 3-bromopropanal (9.0 g, 65.7 mmol), cyclopentyl methyl ether (80 mL), 1-octanol (21.4 g, 164.3 mmol), and ammonium bromide (322 mg, 3.3 mmol) were added. The reaction solution was heated to 130 ° C. and refluxed to separate water under stirring. The reaction was carried out for 6 h. The mixture was filtered, the filtrate was collected, and the mixture was concentrated under reduced pressure to obtain a crude product of 3,3-dioctyloxypropane bromide. The crude product was chromatographed on a silica gel column using n-hexane as eluent to obtain 9.63 g of 3,3-dioctyloxypropane bromide with a yield of 38.6%.

[1174] Step 3: Synthesize 1245-A

[1175] Reaction formula:

[1176] Experimental process:

[1177] 2-Hydroxymethyl-1,3-propanediol (4.5 g, 42.7 mmol) and DMF (250 mL) were added to a 500 mL two-necked flask. The reaction solution was cooled to 0°C with stirring, and sodium hydride (1.5 g, 37.0 mmol) was added in batches. The reaction was continued at 0°C for 1 h. A DMF solution of 3,3-dioctyloxy-1-bromopropane (11.2 g, 29.5 mmol, dissolved in 20 mL of DMF) was slowly added dropwise. After the addition was complete, the reaction solution was heated to 10°C and allowed to react for 6 h. 200 mL of water was added to quench the reaction, and the solution was then transferred to a 1 L separatory funnel. 300 mL of water was added and the solution was extracted twice with 200 mL of ethyl acetate. The organic phases were combined, washed with 300 mL of water, and concentrated under reduced pressure to obtain crude 1245-A. The crude product was eluted with n-hexane:ethyl acetate = 3:1 to obtain 5.87 g of 1245-A, with a yield of 49.2%.

[1178] Step 4: Synthesize 1245-B

[1179] Reaction formula:

[1180] Experimental process:

[1181] 1245-A (5.87 g, 14.0 mmol) and DCM (280 mL) were added to a 500 mL two-necked flask. The reaction solution was cooled to -10°C with stirring, and linoleic acid (4.32 g, 15.4 mmol), EDCI (4.03 g, 21.0 mmol), DMAP (171 mg, 1.4 mmol), and pyridine (1.66 g, 21.0 mmol) were added. After the addition was complete, the reaction was allowed to proceed at -10°C for 8 h. The reaction solution was warmed to room temperature and quenched by adding 200 mL of water. The reaction was then extracted twice with 200 mL of DCM. The organic phases were combined and concentrated under reduced pressure to obtain a crude product of 1245-B. The crude product was eluted with n-hexane:ethyl acetate = 5:1 to obtain 5.6 g of 1245-B, with a yield of 58.7%.

[1182] Step 5: Synthesis of amino lipid compound 1245

[1183] Reaction formula:

[1184] Experimental process:

[1185] To a 250 mL two-necked flask were added 1245-B (4.85 g, 7.12 mmol), DCM (70 mL), DMAP (261 mg, 2.14 mmol), and pyridine (1.41 g, 17.8 mmol), and the mixture was stirred at room temperature. Then, p-nitrophenyl chloroformate (2.87 g, 15.54 mmol) was slowly added in batches, and the reaction was carried out at room temperature for 1 h. 3-diethylamino-1-propanol (2.8 g, 21.4 mmol) was added, and the reaction was carried out at room temperature for 12 h. The solvent was evaporated under reduced pressure, 100 mL of water was added, and the mixture was extracted twice with 100 mL of n-hexane. The organic phases were combined, washed with 150 mL of water, and concentrated under reduced pressure to obtain a crude amino lipid compound 1245. The crude product was eluted by silica gel column chromatography using n-hexane: ethyl acetate = 1:1 to obtain 3.28 g of amino lipid compound 1245, with a yield of 55.0% and a purity of 96.30%.

[1186] LC-MS(ESI):Calculated for(M+H)838.7,Found 839.1.

[1187] Example 4 Synthesis of amino lipid compound 1246

[1188] Step 1: Synthesis of 4-(tert-butyldimethylsilyl)oxy-1-butanol

[1189] Reaction formula:

[1190] Experimental process:

[1191] To a 1 L single-necked flask, 1,4-butanediol (20.0 g, 222 mmol), DCM (660 mL), and imidazole (22.67 g, 333 mmol) were added. The reaction solution was cooled to 0°C with stirring, and TBSCl (36.7 g, 244 mmol) was added. The reaction was continued at 0°C for 6 h, 400 mL of water was added, and the mixture was extracted twice with 300 mL of DCM. The organic phases were combined and concentrated under reduced pressure to give a crude product of 4-(tert-butyldimethylsilyl)oxy-1-butanol. The crude product was chromatographed on a silica gel column using n-hexane:ethyl acetate = 5:1 as the eluent to give 22.5 g of 4-(tert-butyldimethylsilyl)oxy-1-butanol in a yield of 49.5%.

[1192] Step 2: Synthesis of 4-(tert-butyldimethylsilyl)oxy-1-butyraldehyde

[1193] Reaction formula:

[1194] Experimental process:

[1195] To a 1L single-necked flask was added 4-(tert-butyldimethylsilyl)oxo-1-butanol (22.5 g, 110 mmol) and DCM (300 mL). TEMPO (344 mg, 2.2 mmol), potassium bicarbonate (7.7 g, 77 mmol), and sodium bromide (453 mg, 4.4 mmol) were added under stirring. The reaction solution was cooled to 5°C and an aqueous solution of NaDCC (14.5 g, 66 mmol, dissolved in 150 mL of water) was added dropwise. The reaction was continued at 5°C for 3 h, filtered, and the filter cake was washed once with 50 mL of water and 50 mL of DCM. The filtrate was collected, the filtrate was separated, and the organic phase was collected. The aqueous phase was extracted twice with 150 mL of DCM. The organic phases were combined and concentrated under reduced pressure to give a crude product of 4-(tert-butyldimethylsilyl)oxo-1-butanal. The crude product was chromatographed on a silica gel column using DCM as eluent to give 11.4 g of 4-(tert-butyldimethylsilyl)oxo-1-butanal. 4-(tert-Butyldimethylsilyl)oxy-1-butanal, yield 51.2%.

[1196] Step 3: Synthesis of 4,4-dioctyloxy-1-TBS butanol

[1197] Reaction formula:

[1198] Experimental process:

[1199] To a 250 mL single-necked flask was added 4-(tert-butyldimethylsilyl)oxo-1-butanal (10.0 g, 49.4 mmol), cyclopentyl methyl ether (80 mL), 1-octanol (16.1 g, 123.5 mmol), and ammonium bromide (242 mg, 2.47 mmol). The reaction solution was heated to 130° C. under reflux and water separation with stirring. The reaction was continued for 6 h, filtered, and the filtrate was collected and concentrated under reduced pressure to obtain a crude product of 4,4-dioctyloxy-1-TBS butanol. The crude product was chromatographed on a silica gel column using n-hexane as eluent to obtain 10.2 g of 4,4-dioctyloxy-1-TBS butanol with a yield of 46.4%.

[1200] Step 4: Synthesis of 4,4-dioctyloxy-1-butanol

[1201] Reaction formula:

[1202] Experimental process:

[1203] To a 250 mL single-necked flask was added 4,4-dioctyloxy-1-TBS butanol (10.0 g, 22.5 mmol), tetrahydrofuran (110 mL), and TBAF (10.6 g, 33.7 mmol). The mixture was stirred and reacted at room temperature for 6 h. 80 mL of saturated sodium bicarbonate solution was added, followed by extraction twice with 80 mL of ethyl acetate. The organic phases were combined, washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected and concentrated under reduced pressure to give a crude 4,4-dioctyloxy-1-butanol product. The crude product was eluted with n-hexane:ethyl acetate = 5:1 to give 6.5 g of 4,4-dioctyloxy-1-butanol, with a yield of 87.4%.

[1204] Step 5: Synthesize 1246-A1

[1205] Reaction formula:

[1206] Experimental process:

[1207] To a 500 mL two-necked flask were added 5-hydroxymethyl-2,2-dimethyl-1,3-dioxane (13.0 g, 88.9 mmol) and DCM (270 mL). The reaction solution was cooled to -10°C with stirring, and linoleic acid (25.0 g, 88.9 mmol), EDCI (25.6 g, 133.5 mmol), DMAP (2.18 g, 17.8 mmol), and pyridine (10.6 g, 134.0 mmol) were added. The temperature was warmed to room temperature and the reaction was allowed to react for 8 h. The reaction was quenched by adding 200 mL of water and extracted twice with 200 mL of DCM. The organic phases were combined and concentrated under reduced pressure to obtain a crude product of 1246-A1. The crude product was eluted by silica gel column chromatography using n-hexane:ethyl acetate = 20:1 to obtain 23.6 g of 1246-A1, with a yield of 64.9%.

[1208] Step 6: Synthesize 1246-A

[1209] Reaction formula:

[1210] Experimental process:

[1211] To a 1 L round-bottom flask were added 1246-A1 (23.6 g, 57.8 mmol) and ethanol (360 mL). The mixture was stirred at room temperature and hydrochloric acid (120 mL) was added dropwise. The reaction was allowed to react at room temperature for 1 h. The reaction was quenched by adding 600 mL of saturated sodium bicarbonate solution and extracted twice with 500 mL of DCM. The organic phases were combined and concentrated under reduced pressure to give the crude product 1246-A. The crude product was eluted with n-hexane:ethyl acetate = 3:1 to obtain 17.5 g of 1246-A, a yield of 82.2%.

[1212] Step 7: Synthesis of 1246-A-TBS

[1213] Reaction formula:

[1214] Experimental process:

[1215] To a 1 L round-bottom flask, 1246-A (21.3 g, 57.8 mmol) and DCM (600 mL) were added. The reaction solution was cooled to 0°C with stirring, and imidazole (5.9 g, 86.7 mmol) and TBSCl (9.6 g, 63.7 mmol) were added. The reaction was carried out at 0°C for 8 h. The reaction was quenched by adding 500 mL of saturated sodium bicarbonate solution and extracted twice with DCM (500 mL). The organic phases were combined, washed with 400 mL of saturated sodium chloride solution, and concentrated under reduced pressure to give the crude product. The crude product was eluted by silica gel column chromatography with n-hexane:ethyl acetate = 10:1 to obtain 12.4 g of 1246-A-TBS, with a yield of 44.4%.

[1216] Step 8: Synthesize 1246-B

[1217] Reaction formula:

[1218] Experimental process:

[1219] To a 100 mL two-necked flask was added 1246-A-TBS (4.5 g, 9.32 mmol), DCM (45 mL), and DMAP (0.34 g, 2.79 mmol). Pyridine (1.62 g, 20.5 mmol) was added dropwise with stirring, and p-nitrophenyl chloroformate (3.75 g, 18.6 mmol) was slowly added in batches. The reaction was carried out at room temperature for 1 h. A mixture of 3-diethylamino-1-propanol (3.66 g, 27.9 mmol) and triethylamine (0.93 g, 9.32 mmol) was added and the reaction was carried out at room temperature for 16 h. The solvent was evaporated under reduced pressure, 200 mL of water was added, and the mixture was extracted twice with 200 mL of n-hexane. The organic phases were combined, washed with 200 mL of water and 150 mL of saturated sodium bicarbonate solution, and concentrated under reduced pressure to obtain 5.72 g of an oil.

[1220] The above oil (5.72 g) and tetrahydrofuran (57 mL) were added to a 250 mL round-bottom flask, stirred at room temperature, and triethylamine trihydrofluoride (14.35 g) was added dropwise. The reaction was allowed to react at room temperature for 16 h. The reaction solution was concentrated and diluted with 100 mL of ethyl acetate. The pH was adjusted to 8 with saturated sodium bicarbonate solution, and the mixture was washed with 200 mL of water. The aqueous phase was extracted twice with 200 mL of ethyl acetate. The organic phases were combined and concentrated under reduced pressure to obtain crude 1246-B. The crude product was eluted with DCM:methanol in a ratio of 10:1 to obtain 960 mg of 1246-B, a yield of 19.6%.

[1221] Step 9: Synthesize 1246-C

[1222] Reaction formula:

[1223] Experimental process:

[1224] To a 25 mL single-necked flask were added 4,4-dioctyloxy-1-butanol (1.0 g, 3.02 mmol), DCM (10 mL), DMAP (74 mg, 0.6 mmol), and pyridine (0.36 g, 4.5 mmol). The mixture was stirred at room temperature, and p-nitrophenyl chloroformate (0.91 g, 4.5 mmol) was slowly added portionwise. The reaction was allowed to react at room temperature for 1 h. The reaction solution was concentrated, 100 mL of water was added, and the mixture was extracted twice with 100 mL of n-hexane. The organic phases were combined, washed with 150 mL of water and 150 mL of saturated sodium bicarbonate solution, and concentrated under reduced pressure to obtain a crude product of 1246-C. The crude product was eluted with n-hexane:ethyl acetate = 1:1 to obtain 905 mg of 1246-C, with a yield of 60.3%.

[1225] Step 10: Synthesis of amino lipid compound 1246

[1226] Reaction formula:

[1227] Experimental process:

[1228] To a 25 mL two-necked flask were added 1246-B (0.96 g, 1.82 mmol), DCM (10 mL), DMAP (67 mg, 0.55 mmol), and triethylamine (0.45 mL, 3.65 mmol), and the mixture was stirred at room temperature. 1246-C (0.91 g, 1.82 mmol) was added, and the reaction was allowed to react at room temperature for 12 h. 100 mL of water was added, and the mixture was extracted with 50 mL of DCM. The aqueous phase was extracted twice with 100 mL of DCM. The organic phases were combined, washed with 150 mL of saturated sodium bicarbonate solution, and concentrated under reduced pressure to obtain the crude amino lipid compound 1246. The crude product was eluted with n-hexane:ethyl acetate = 1:1 to obtain 1.25 g of amino lipid compound 1246, with a yield of 77.6% and a purity of 94.13%.

[1229] 1H NMR (600MHz, CDCl3) δ5.41-5.29(m,4H),4.47(t,J=5.5Hz,1H),4.22-4.12(m,10H),3.55(dt,J=9.2, 6.7Hz,2H),3.40(dt,J=9.2,6.7Hz,2H),2.76(t,J=6.9Hz,2H),2.50(q,J=7.2Hz,6H),2.45(dt,J=11. 9,5.9Hz,1H),2.30(t,J=7.6Hz,2H),2.04(q,J=7.0Hz,4H),1.84-1.77(m,2H),1.77-1.64(m,4H),1. 63-1.58(m,2H),1.58-1.51(m,4H),1.39-1.20(m,34H),1.00(t,J=7.1Hz,6H),0.88(q,J=6.9Hz,9H).

[1230] 13 C NMR (151MHz, CDCl3) δ173.60,155.13,155.11,130.36,130.18,128.18,128.0 5,102.70,68.30,67.12,66.00,65.03,65.00,61.39,49.21,47.01,37.75,34 .23,31.98,31.66,30.02,29.93,29.75,29.58,29.49,29.41,29.32,29.26,27.34,26.60,26.40,25.77,24.98,24.20,22.80,22.71,14.24,14.22,11.87.

[1231] LC-MS(ESI):Calculated for(M+H)882.7,Found 883.1.

[1232] Example 5 Synthesis of amino lipid compound 1247

[1233] According to the general synthesis method and the method of Example 3, the amino lipid compound 1247 was prepared according to the following reaction scheme to obtain 2.0 g of the amino lipid compound 1247 with a yield of 54.9% and a purity of 95.75%.

[1234] 1H NMR (600MHz, CDCl3) δ5.41-5.29(m,4H),4.58(t,J=5.8Hz,1H),4.22-4.14(m,5H),4.11(dd,J=11.1,6.4Hz ,1H),3.56(dt,J=9.2,6.7Hz,2H),3.46(dd,J=13.7,6.1Hz,4H),3.40(dt,J=9.3,6.7Hz,2H),2.77(t,J=6.9 Hz,2H),2.62-2.49(m,6H),2.33-2.28(m,3H),2.04(q,J=7.0Hz,4H),1.85(q,J=6.2Hz,2H),1.83-1.78(m,2 H),1.63-1.58(m,2H),1.58-1.52(m,4H),1.38-1.22(m,34H),1.00(t,J=7.1Hz,6H),0.88(q,J=7.0Hz,9H).

[1235] 13 C NMR (151MHz, CDCl3) δ173.74,155.31,130.36,130.18,128.19,128.05,100. 79,68.34,67.59,66.95,66.28,66.27,65.88,62.18,49.23,47.01,38.65,34 .33,34.09,31.99,31.67,30.07,29.76,29.60,29.49,29.44,29.34,29.29,29.28,27.34,26.62,26.42,25.77,25.05,22.81,22.72,14.24,14.22,11.88.

[1236] LC-MS(ESI):Calculated for(M+H)824.7,Found 825.1.

[1237] Example 6 Synthesis of amino lipid compound 1248

[1238] According to the general synthesis method and the method of Example 3, amino lipid compound 1248 was prepared according to the following reaction scheme to obtain 5.47 g of amino lipid compound 1248 with a yield of 82.6% and a purity of 96.52%.

[1239] 1H NMR (600MHz, CDCl3) δ5.41-5.19(m,4H),4.44(t,J=5.7Hz,1H),4.23-4.14(m,5H),4.11(dd, J=11.2,6.4Hz,1H),3.55(dt,J=9.2,6.7Hz,2H),3.44(d,J=5.9Hz,2H),3. 42-3.36(m,4H),2.77(t,J=6.8Hz,2H),2.62-2.49(m,6H),2.33-2.28(m,3 H),2.04(q,J=7.0Hz,4H),1.83-1.77(m,2H),1.63-1.58(m,4H),1.58-1.5 2(m,6H),1.41-1.21(m,36H),1.00(t,J=7.1Hz,6H),0.88(q,J=6.9Hz,9H).

[1240] 13 C NMR (151MHz, CDCl3) δ173.75,155.31,130.36,130.18,128.18,128.05,103. 14,71.44,68.26,66.93,65.93,65.73,62.23,49.23,47.02,38.69,34.34,33 .42,31.99,31.67,30.06,29.76,29.59,29.57,29.49,29.43,29.34,29.28,27.34,26.62,26.42,25.77,25.05,22.81,22.72,21.52,14.25,14.22,11.89.

[1241] LC-MS(ESI):Calculated for(M+H)852.7,Found 853.1.

[1242] Example 7 Synthesis of amino lipid compound 387

[1243] According to the general synthesis method, compound 387-A5 was substituted for 383-D, and the amino lipid compound 387 was synthesized according to the fourth step of Example 1, wherein 387-A5 (1.7 g, 1.76 mmol) and 3-diethylamino-1-propanol (1.39 g, 10.56 mmol) were used to obtain 0.37 g of amino lipid compound 387 with a yield of 21.93% and a purity of 95.40%.

[1244] 1H NMR (600MHz, CDCl3) δ4.67(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.5Hz,2H) ,4.07(t,J=6.2Hz,4H),3.56(dt,J=9.3,6.7Hz,4H),3.40(dt,J=9.3,6.7Hz,4H) ,2.55-2.47(m,6H),2.28(t,J=7.6Hz,4H),1.85-1.76(m,2H),1.74-1.63(m,8H ),1.63-1.48(m,16H),1.38-1.20(m,36H),1.00(t,J=7.1Hz,6H),0.90(m,12H).

[1245] LC-MS(ESI):Calculated for(M+H)958.79,Found 959.3.

[1246] Example 8 Synthesis of amino lipid compound 388

[1247] According to the general synthesis method, compound 388-A5 was substituted for 383-D, and the amino lipid compound 388 was synthesized according to the fourth step of Example 1, wherein 388-A5 (1.2 g, 1.17 mmol) and 3-dimethylamino-1-propanol (0.72 g, 7.02 mmol) were used to obtain 0.37 g of amino lipid compound 388 with a yield of 31.95% and a purity of 94.45%.

[1248] 1 H NMR (600MHz, CDCl3) δ4.71-4.63(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.6Hz ,2H),4.08(t,J=6.2Hz,4H),3.57(dt,J=9.3,6.7Hz,4H),3.41(dt,J=9.3,6.7Hz ,4H),2.39-2.34(m,2H),2.28(t,J=7.6Hz,4H),2.22(s,6H),1.88-1.80(m,2H), 1.74-1.63(m,10H),1.63-1.47(m,16H),1.39-1.22(m,42H),0.95-0.81(m,12H).

[1249] LC-MS(ESI):Calculated for(M+H)986.82,Found 987.4.

[1250] Example 9 Synthesis of amino lipid compound 389

[1251] According to the general synthesis method, compound 389-A5 was substituted for 383-D, and the amino lipid compound 389 was synthesized according to the fourth step of Example 1, wherein 389-A5 (2.4 g, 2.23 mmol) and 3-diethylamino-1-propanol (1.75 g, 13.35 mmol) were used to obtain 1.05 g of amino lipid compound 389 with a yield of 43.97% and a purity of 92.22%.

[1252] 1 H NMR (600MHz, CDCl3) δ4.72-4.62 (m, 1H), 4.45 (t, J = 5.7Hz, 2H), 4.17 (t, J = 6. 5Hz,2H),4.05(t,J=6.7Hz,4H),3.56(dt,J=9.3,6.7Hz,4H),3.40(dt,J=9.3, 6.7Hz,4H),2.61-2.43(m,6H),2.28(t,J=7.6Hz,4H),1.87-1.76(m,2H),1.5 7(m,26H),1.43-1.16(m,50H),1.01(t,J=7.1Hz,6H),0.89(t,J=6.9Hz,12H).

[1253] LC-MS(ESI):Calculated for(M+H)1070.67,Found.

[1254] Example 10 Synthesis of amino lipid compound 390

[1255] According to the general synthesis method, compound 390-A5 was substituted for 383-D, and the amino lipid compound 390 was synthesized according to the fourth step of Example 1, wherein 390-A5 (1.2 g, 1.17 mmol) and 3-diethylamino-1-propanol (0.92 g, 7.02 mmol) were used to obtain 0.44 g of amino lipid compound 390 with a yield of 37.06% and a purity of 91.06%.

[1256] 1H NMR (600MHz, CDCl3) δ4.71-4.61(m,1H),4.45(t,J=5.7Hz,2H),4.17(t,J=6.5 Hz, 2H), 4.05 (t, J = 6.7Hz, 4H), 3.56 (dt, J = 9.3, 6.7Hz, 4H), 3.40 (dt, J = 9.3, 6. 7Hz,4H),2.51(td,J=7.1,3.4Hz,6H),2.28(t,J=7.6Hz,4H),1.85-1.76(m,2H) ,1.76-1.47(m,26H),1.43-1.17(m,42H),1.01(t,J=7.1Hz,6H),0.90(m,12H).

[1257] LC-MS(ESI):Calculated for(M+H)1014.85,Found 1015.3.

[1258] Example 11 Synthesis of amino lipid compound 391

[1259] According to the general synthesis method, compound 391-A5 was substituted for 383-D, and the amino lipid compound 391 was synthesized according to the fourth step of Example 1, wherein 391-A5 (2 g, 2.03 mmol) and 3-diethylamino-1-propanol (1.6 g, 12.18 mmol) were used to obtain 0.847 g of amino lipid compound 391 with a yield of 43.53% and a purity of 92.68%.

[1260] 1 H NMR (600MHz, CDCl3) δ4.71-4.61(m,1H),4.45(t,J=5.7Hz,2H),4.17(t,J=6.5 Hz, 2H), 4.05 (t, J = 6.7Hz, 4H), 3.56 (dt, J = 9.3, 6.7Hz, 4H), 3.40 (dt, J = 9.3, 6. 7Hz,4H),2.51(td,J=7.1,3.4Hz,6H),2.28(t,J=7.6Hz,4H),1.85-1.76(m,2H) ,1.76-1.47(m,26H),1.43-1.17(m,34H),1.01(t,J=7.1Hz,6H),0.90(m,12H).

[1261] LC-MS(ESI):Calculated for(M+H)958.46,Found 959.1.

[1262] Example 12 Synthesis of amino lipid compound 392

[1263] According to the general synthesis method, compound 392-A5 was substituted for 383-D, and amino lipid compound 392 was synthesized according to the fourth step of Example 1, wherein 392-A5 (0.86 g, 0.85 mmol) and 3-diethylamino-1-propanol (0.67 g, 5.1 mmol) were used to obtain 0.29 g of amino lipid compound 392 with a yield of 33.9% and a purity of 97.93%.

[1264] 1 H NMR(600MHz, CDCl3)δ5.62-5.48(m,8H),4.69-4.65(m,1H),4.62-4.53(m,2H), 4.20-4.11(m,6H),4.09-4.06(m,8H),2.54-2.45(m,6H),2.28(t,J=7.6Hz,4H) ,2.06-2.03(m,8H),1.84-1.76(m,2H),1.75-1.66(m,8H),1.64-1.46(m,8H),1 .43-1.35(m,8H),1.35-1.22(m,20H),1.00(t,J=7.1Hz,6H),0.90(t,J=7.4Hz, 12H).

[1265] LC-MS(ESI):Calculated for(M+H)1006.50,Found 1007.1.

[1266] Example 13 Synthesis of amino lipid compound 396

[1267] According to the general synthesis method, compound 396-A5 was substituted for 383-D, and amino lipid compound 396 was synthesized according to the fourth step of Example 1, wherein 396-A5 (1.3 g, 1.27 mmol) and 1-(3-hydroxypropyl)pyrrolidine (0.67 g, 5.18 mmol) were used to obtain 0.29 g of amino lipid compound 396 with a yield of 22.55% and a purity of 95.18%.

[1268] 1H NMR (600MHz, CDCl3) δ4.71-4.62(m,1H),4.48(t,J=5.2Hz,2H),4.18(t,J=6.6 Hz,2H),4.07(t,J=6.1Hz,4H),3.56(dt,J=9.3,6.7Hz,4H),3.40(dt,J=9.3,6 .7Hz,4H),2.55-2.49(m,6H),2.28(t,J=7.6Hz,4H),1.92-1.97(m,2H),1.80- 1.63(m,14H),1.63-1.45(m,16H),1.43-1.16(m,42H),0.89(t,J=6.9Hz,12H).

[1269] LC-MS(ESI):Calculated for(M+H)1012.55,Found 1013.2.

[1270] Example 14 Synthesis of amino lipid compound 398

[1271] According to the general synthesis method, compound 398-A5 was substituted for 383-D, and the amino lipid compound 398 was synthesized according to the fourth step of Example 1, wherein 398-A5 (1 g, 0.98 mmol) and N-methyl-2-(2-hydroxyethyl)pyrrolidine (0.76 g, 5.88 mmol) were used to obtain 0.29 g of amino lipid compound 398 with a yield of 29.23% and a purity of 96.77%.

[1272] 1 H NMR (600MHz, CDCl3) δ4.72-4.62(m,1H),4.48(d,J=5.3Hz,2H),4.25-4.18(m,1H),4.18- 4.12(m,1H),4.07(t,J=6.0Hz,4H),3.56(dt,J=8.5,6.7Hz,4H),3.40(dt,J=8.9,6.8Hz,4 H),3.05(t,J=8.6Hz,1H),2.28(dd,J=16.8,9.3Hz,7H),2.20-2.02(m,3H),2.00-1.94(m, 1H),1.83-1.63(m,12H),1.63-1.43(m,18H),1.40-1.19(m,42H),0.88(t,J=6.9Hz,12H).

[1273] LC-MS(ESI):Calculated for(M+H)1012.55,Found 1013.2.

[1274] Example 15 Synthesis of amino lipid compound 399

[1275] According to the general synthesis method, compound 399-A5 was substituted for 383-D, and the amino lipid compound 399 was synthesized according to the fourth step of Example 1, wherein 399-A5 (1 g, 0.98 mmol) and 3-(2-methylpiperidin-1-yl)propan-1-amine (0.92 g, 5.88 mmol) were used to obtain 0.7 g of amino lipid compound 399 with a yield of 68.71% and a purity of 96.77%.

[1276] 1 H NMR (600MHz, CDCl3) δ4.69 (s, 1H), 4.48-4.47 (m, 2H), 4.08-4.06 (t, J = 5.9Hz, 4H), 3.56 (dt,J=13.6,6.7Hz,4H),3.40(dt,J=13.8,6.8Hz,4H),3.32-3.21(m,1H),3.17-3.16(m, 1H),2.85-2.83(m,1H),2.79-2.74(m,1H),2.28(t,J=7.5Hz,6H),2.06(t,J=10.7Hz,1H) ,1.81-1.41(m,30H),1.37-1.27(m,46H),1.04(d,J=6.2Hz,3H),0.89(t,J=6.8Hz,12H).

[1277] LC-MS(ESI):Calculated for(M+H)1039.62,Found 1040.3

[1278] Example 16 Synthesis of amino lipid compound 416

[1279] According to the general synthesis method, compound 416-A5 was substituted for 383-D, and amino lipid compound 416 was synthesized according to the fourth step of Example 1, wherein 416-A5 (1 g, 0.98 mmol) and 1-methylpiperidine-3-methanol (0.76 g, 5.88 mmol) were used to obtain 0.6 g of amino lipid compound 416 with a yield of 60.47% and a purity of 96.77%.

[1280] 1H NMR (600MHz, CDCl3) δ4.70-4.62(m,1H),4.48(t,J=5.2Hz,2H),4.08-4.03(m,5H),3.9 4(dd,J=10.6,7.4Hz,1H),3.56(dt,J=9.2,6.7Hz,4H),3.40(dt,J=9.2,6.7Hz,4H),2. 85(d,J=10.2Hz,1H),2.74(d,J=10.5Hz,1H),2.29-2.25(m,7H),2.06-1.94(m,1H),1. 90(t,J=10.8Hz,1H),1.80-1.44(m,29H),1.42-1.08(m,44H),0.89(t,J=6.9Hz,12H).

[1281] LC-MS(ESI):Calculated for(M+H)1012.55,Found 1013.2

[1282] Example 17 Synthesis of amino lipid compound 423

[1283] According to the general synthesis method, compound 423-A5 was substituted for 383-D, and the amino lipid compound 423 was synthesized according to the fourth step of Example 1, wherein 423-A5 (1 g, 0.98 mmol) and 3-dimethylamino-2,2-dimethyl-1-propanol (0.77 g, 5.88 mmol) were used to obtain 0.7 g of amino lipid compound 423 with a yield of 70.4% and a purity of 91.78%.

[1284] 1 H NMR (600MHz, CDCl3) δ4.72-4.63(m,1H),4.48(t,J=5.2Hz,2H),4.08(t,J=6.1Hz,4H),3.94(s,2H),3.57(dt,J=9.1,6.7Hz,4H),3.41 (dt,J=9.2,6.7Hz,4H),2.30-2.23(m,10H),2.17(s,2H),1.75-1.47(m,26H),1.42-1.17(m,42H),0.92(s,6H),0.89(t,J=6.9Hz,12H)

[1285] LC-MS(ESI):Calculated for(M+H)1014.57,Found 1015.2

[1286] Example 18 Synthesis of amino lipid compound 429

[1287] According to the general synthesis method, compound 429-A5 was substituted for 383-D, and amino lipid compound 429 was synthesized according to the fourth step of Example 1, wherein 429-A5 (2 g, 1.94 mmol) and 3-diethylamino-1-propanol (1.53 g, 11.64 mmol) were used to obtain 0.84 g of amino lipid compound 429 with a yield of 42.35% and a purity of 97.22%.

[1288] 1 H NMR (600MHz, CDCl3) δ4.71-4.62(m,1H),4.48(t,J=5.1Hz,2H),4.17(t,J=6.5Hz, 2H),4.07(t,J=6.0Hz,4H),3.67(dt,J=9.3,6.3Hz,4H),3.55-3.36(m,20H),2.53 (td,J=7.1,3.4Hz,6H),2.28(t,J=7.6Hz,4H),1.86-1.81(m,10H),1.73-1.63(m, 8H),1.63-1.45(m,8H),1.27(m,20H),1.19(t,J=7.0Hz,12H),1.03-1.00(m,6H).

[1289] LC-MS(ESI):Calculated for(M+H)1022.45,Found 1023.1

[1290] Example 19 Synthesis of amino lipid compound 430

[1291] According to the general synthesis method, compound 430-A5 was substituted for 383-D, and amino lipid compound 430 was synthesized according to the fourth step of Example 1, wherein 430-A5 (2.3 g, 1.7 mmol) and 3-diethylamino-1-propanol (1.34 g, 10.2 mmol) were used to obtain 0.84 g of amino lipid compound 430 with a yield of 36.7% and a purity of 98.29%.

[1292] 1H NMR (600MHz, CDCl3) δ4.70-4.63(m,1H),4.43(t,J=5.2Hz,2H),4.17(t,J=6.5 Hz, 2H), 4.07 (t, J=6.2Hz, 4H), 3.46 (dd, J=9.2, 5.8Hz, 4H), 3.27 (dd, J=9.2, 5. 8Hz,4H),2.57-2.45(m,6H),2.28(t,J=7.6Hz,4H),1.86-1.76(m,2H),1.74-1. 45(m,24H),1.42-1.18(m,80H),1.01(t,J=7.1Hz,6H),0.89(q,J=6.9Hz,24H).

[1293] LC-MS(ESI):Calculated for(M+H)1351.21,Found 1351.8

[1294] Example 20 Synthesis of amino lipid compound 490

[1295] According to the general synthesis method, compound 490-A5 was used to replace 383-D, and the amino lipid compound 490 was synthesized according to the fourth step of Example 1, wherein 490-A5 (2.9 g, 2.69 mmol) and 3-dimethylamino-1-propanol (1.67 g, 16.14 mmol) were used to obtain 1.3 g of amino lipid compound 490 with a yield of 46.35% and a purity of 93.50%.

[1296] 1 H NMR (600MHz, CDCl3) δ4.67(s,1H),4.47(t,J=5.3Hz,2H),4.17(t,J=6.6Hz,2H),4. 07(t,J=6.2Hz,4H),3.56(dt,J=9.3,6.7Hz,4H),3.40(dt,J=9.3,6.7Hz,4H),2.37- 2.34(m,2H),2.28(t,J=7.6Hz,4H),2.22(s,6H),1.87-1.81(m,2H),1.68(t,J=6.6H z,12H),1.56(dt,J=14.5,4.6Hz,12H),1.34-1.24(m,52H),0.88(t,J=7.0Hz,12H).

[1297] LC-MS(ESI): Calculated for 1042.62, Found(M+H): 1043.4.

[1298] Example 21 Synthesis of amino lipid compound 849

[1299] According to the general synthesis method, compound 849-A5 was used to replace 383-D, and the amino lipid compound 849 was synthesized according to the fourth step of Example 1, wherein 849-A5 (2.0 g, 1.68 mmol) and 3-dimethylamino-1-propanol (1.04 g, 10.08 mmol) were used to obtain 0.8 g of amino lipid compound 849 with a yield of 41.2% and a purity of 93.97%.

[1300] 1 H NMR (600MHz, CDCl3) δ4.66(m,1H),4.47(t,J=5.2Hz,2H),4.17(t,J=6.6Hz,2H) ,4.07(t,J=6.1Hz,4H),3.55(dt,J=9.2,6.7Hz,4H),3.40(dt,J=9.2,6.7Hz,4H) ,2.38-2.33(m,2H),2.27(t,J=7.6Hz,4H),2.22(s,6H),1.87-1.80(m,2H),1.7 1-1.63(m,8H),1.63-1.49(m,16H),1.37-1.20(m,66H),0.87(t,J=7.0Hz,12H).

[1301] LC-MS(ESI):Calculated for(M+H)1154.84,Found 1155.5.

[1302] Example 22 Synthesis of amino lipid compound 859

[1303] According to the general synthesis method, compound 859-A5 was used to replace 383-D, and the amino lipid compound 859 was synthesized according to the fourth step of Example 1, wherein 859-A5 (1.1 g, 0.97 mmol) and 3-diethylamino-1-propanol (0.76 g, 5.82 mmol) were used to obtain 270 mg of amino lipid compound 859 with a yield of 24.72% and a purity of 95.67%.

[1304] 1H NMR (600MHz, CDCl3) δ4.72-4.59(m,1H),4.48(t,J=5.1Hz,2H),4.17(t,J=6.5Hz,2H ),4.08(t,J=6.1Hz,4H),3.56(dt,J=9.1,6.7Hz,4H),3.40(dt,J=9.1,6.7Hz,4H),2 .51(td,J=7.1,3.4Hz,6H),2.28(t,J=7.6Hz,4H),1.84-1.77(m,2H),1.73-1.50(m, 28H), 1.31 (dd, J=30.6, 6.5Hz, 56H), 1.01 (t, J=7.1Hz, 6H), 0.88 (t, J=7.0Hz, 12H).

[1305] LC-MS(ESI): Calculated for 1126.78, Found(M+H): 1127.4.

[1306] Example 23 Synthesis of amino lipid compound 2021

[1307] Step 1: Synthesize 2021-A2

[1308] Take EDCI (8.0 g, 41.75 mmol), add DCM (120 ml), TEA (4.18 g, 41.75 mmol), add 2021-A1 (9.6 g, 33.4 mmol) under stirring at room temperature, after the reaction solution is clarified, add 2-hydroxymethyl-1,3-propanediol (1.8 g, 16.7 mmol) and DMAP (377 mg, 3.09 mmol), and react at room temperature for 16 hours. The reaction solution is washed with saturated potassium bicarbonate solution (150 ml), separated, and the organic phase is collected. The aqueous phase is extracted once with DCM (80 ml). The organic phases are combined and the solvent is evaporated under reduced pressure to obtain the crude product of 2021-A2. The crude product is chromatographed on a silica gel column and eluted with n-hexane:ethyl acetate = 20:1 to obtain 4.5 g of 2021-A2, with a yield of 41.65%.

[1309] Step 2: Synthesize 2021-A3

[1310] To a 50 mL single-necked round-bottom flask, 2012-A2 (2.0 g, 3.09 mmol) was added and dissolved in DCM (20 mL). DMAP (113 mg, 0.93 mmol) and pyridine (0.61 g, 7.73 mmol) were added, and the mixture was stirred at room temperature. p-Nitrophenyl chloroformate (1.25 g, 6.18 mmol) was added portionwise, and stirring was continued for 1 h. The mixture was diluted with water (150 mL) and extracted with DCM (100 mL). The organic phase was collected, washed with water (80 mL), and concentrated to give 3.5 g of crude 2021-A3. The crude product was eluted by silica gel column chromatography using ethyl acetate:n-heptane = 1.5:1 to give 2.13 g of 2021-A3, with a yield of 85%.

[1311] Step 3: Synthesize 2021

[1312] To a 50 mL single-necked round-bottom flask, 2021-A3 (2.0 g, 2.46 mmol) was added, dissolved in DCM (20 mL), and DMAP (92 mg, 0.75 mmol), triethylamine (0.75 mg, 7.38 mmol), and dimethylaminopropanol (1.52 g, 14.76 mmol) were added. The mixture was stirred at room temperature for 2 days, diluted with water (100 mL), and extracted with dichloromethane (100 mL). The organic phase was collected, washed with water (80 mL), and concentrated under reduced pressure to obtain 2.6 g of crude 2021. The crude product was eluted with ethyl acetate: n-heptane = 1.5:1 to obtain 1.16 g of amino lipid compound 2021, with a yield of 61% and a purity of 95.32%.

[1313] 1 H NMR(600MHz, CDCl3) δ4.47(t,J=5.6Hz,2H),4.18(t,J=6.1Hz,4H),4.13(dd,J= 6.0,1.8Hz,4H),3.55(dt,J=9.3,6.7Hz,4H),3.39(dt,J=9.3,6.7Hz,4H),2.43 -2.37(m,5H),2.36-2.32(m,2H),2.21(s,6H),1.91(td,J=7.6,5.7Hz,4H),1.8 5-1.80(m,2H),1.57-1.51(m,8H),1.35-1.24(m,24H),0.88(t,J=7.0Hz,12H).

[1314] LC-MS(ESI): Calculated for 776.11, Found(M+H): 776.7.

[1315] Example 24 Synthesis of amino lipid compound 2035

[1316] According to the general synthesis method, compound 2035-A5 was used to replace 383-D, and the amino lipid compound 2035 was synthesized according to the fourth step of Example 1, wherein 2035-A5 (4.1 g, 4.12 mmol) and 3-dimethylamino-1-propanol (2.55 g, 24.6 mmol) were used to obtain 3.0 g of amino lipid compound 2035 with a yield of 75.97% and a purity of 92.02%.

[1317] 1 H NMR (600MHz, CDCl3) δ4.71-4.63(m,1H),4.60(t,J=5.8Hz,2H),4.23-4.10(m,6H),3.58(dt,J=9.2,6.7Hz,4H),3.42(dt,J=9.2,6.7Hz,4H),2. 47-2.38(m,2H),2.32-2.24(m,10H),1.94(q,J=6.4Hz,4H),1.90-1.81( m,2H),1.63-1.49(m,16H),1.38-1.22(m,44H),0.89(t,J=7.0Hz,12H).

[1318] LC-MS(ESI):Calculated for(M+H)958.46,Found 959.2.

[1319] Example 25 Synthesis of amino lipid compound 2036

[1320] According to the general synthesis method, compound 2036-A5 was used to replace 383-D, and the amino lipid compound 2036 was synthesized according to the fourth step of Example 1, wherein 2036-A5 (4.85 g, 4.62 mmol) and 3-dimethylamino-1-propanol (2.86 g, 27.7 mmol) were used to obtain 0.9 g of amino lipid compound 2036 with a yield of 19.2% and a purity of 92.23%.

[1321] 1H NMR (600MHz, CDCl3) δ4.67(m,1H),4.46(t,J=5.7Hz,2H),4.17(t,J=6.6Hz,2 H),4.06(t,J=6.7Hz,4H),3.56(dt,J=9.3,6.7Hz,4H),3.40(dt,J=9.3,6.7Hz ,4H),2.39-2.34(m,2H),2.28(t,J=7.6Hz,4H),2.22(s,6H),1.84(dd,J=14.2 ,7.1Hz,2H),1.66-1.54(m,30H),1.45-1.27(m,42H),0.89(t,J=7.0Hz,12H).

[1322] LC-MS(ESI):Calculated for(M+H)1014.57,Found 1015.3.

[1323] Example 26 Synthesis of amino lipid compound 2038

[1324] According to the general synthesis method, compound 2038-A5 was used to replace 383-D, and the amino lipid compound 2038 was synthesized according to the fourth step of Example 1, wherein 2038-A5 (0.91 g, 1.02 mmol) and 3-dimethylamino-1-propanol (0.63 g, 6.12 mmol) were used to obtain 425 mg of amino lipid compound 2038 with a yield of 47.77% and a purity of 94.67%.

[1325] 1 H-NMR (600MHz, CDCl3) δ4.70-4.63(m,1H),4.48(t,J=5.2Hz,2H),4.22(t,J=5.8Hz,2H),4.07(t,J=6.2Hz,4H),3.57(dt,J=9.2,6.7Hz,4H),3.41 (dt,J=9.2,6.7Hz,4H),2.65-2.57(m,4H),2.30(ddd,J=15.3,11.8,6.9H z,14H),1.70-1.54(m,20H),1.38-1.27(m,28H),0.89(t,J=6.9Hz,12H).

[1326] LC-MS(ESI): Calculated for 874.29, Found(M+H): 875.1.

[1327] Example 27 Synthesis of Amino Lipid Compound 2039

[1328] According to the general synthesis method, compound 2039-A5 was used to replace 383-D, and the amino lipid compound 2039 was synthesized according to the fourth step of Example 1, wherein 2039-A5 (5.0 g, 5.33 mmol) and 3-dimethylamino-1-propanol (3.3 g, 31.97 mmol) were used to obtain 1.05 g of amino lipid compound 2039 with a yield of 21.83% and a purity of 94.51%.

[1329] 1 H NMR (600MHz, CDCl3) δ4.67(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.6Hz,2H),4 .08(t,J=6.2Hz,4H),3.57(dt,J=9.3,6.7Hz,4H),3.41(dt,J=9.3,6.7Hz,4H),2. 38-2.35(m,2H),2.31-2.26(m,4H),2.23(s,6H),1.85(dt,J=13.8,6.7Hz,4H),1. 73-1.65(m,8H),1.58(m,16H),1.57–1.39-1.25(m,30H),0.89(t,J=7.0Hz,12H).

[1330] LC-MS(ESI): Calculated for 902.35, Found(M+H): 903.30.

[1331] Example 28 Synthesis of amino lipid compound 2040

[1332] According to the general synthesis method, compound 2040-A5 was used to replace 383-D, and the amino lipid compound 2040 was synthesized according to the fourth step of Example 1, wherein 2040-A5 (2.0 g, 2.07 mmol) and 3-dimethylamino-1-propanol (1.28 g, 12.42 mmol) were used to obtain 0.77 g of amino lipid compound 2040 with a yield of 40.0% and a purity of 92.49%.

[1333] 1H NMR (600MHz, CDCl3) δ4.68(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.6Hz,2H),4.08(t,J=6.2Hz,4 H),3.57(dt,J=9.3,6.7Hz,4H),3.41(dt,J=9.3,6.7Hz,4H),2.38-2.35(m,2H),2.31-2.26(m,4H), 2.23(s,6H),1.85(dt,J=13.8,6.7Hz,4H),1.73-1.65(m,8H),1.58(m,16H),1.39-1.25(m,34H),0.89(t,J=7.0Hz,12H).

[1334] LC-MS(ESI): Calculated for 930.40, Found(M+H): 931.2.

[1335] Example 29 Synthesis of amino lipid compound 2041

[1336] According to the general synthesis method, compound 2041-A5 was used to replace 383-D, and the amino lipid compound 2041 was synthesized according to the fourth step of Example 1, wherein 2041-A5 (2.5 g, 2.51 mmol) and 3-dimethylamino-1-propanol (1.56 g, 15.08 mmol) were used to obtain 0.66 g of amino lipid compound 2041 with a yield of 27.43% and a purity of 91.97%.

[1337] 1 H NMR (600MHz, CDCl3) δ4.68(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.6Hz,2H),4.07(t,J=6.2Hz,4H),3.41(dt,J=9.3,6.7Hz,4H),2.56-2.46(m ,6H),2.32-2.24(m,4H),1.71-1.66(m,12H),1.62(m,4H),1.59-1.54(m, 10H),1.40-1.25(m,40H),1.01(t,J=7.1Hz,6H),0.89(t,J=7.0Hz,12H).

[1338] LC-MS(ESI):Calculated for(M+H)958.46,Found 959.0.

[1339] Example 30 Synthesis of amino lipid compound 2042

[1340] According to the general synthesis method, compound 2038-A5 was used to replace 383-D, and the amino lipid compound 2042 was synthesized according to the fourth step of Example 1, wherein 2038-A5 (1.0 g, 1.10 mmol) and 3-diethylamino-1-propanol (0.86 g, 6.60 mmol) were used to obtain 0.35 g of amino lipid compound 2042 with a yield of 35.26% and a purity of 96.36%.

[1341] 1 H NMR (600MHz, CDCl3) δ4.68(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.6Hz,2H) ,4.07(t,J=6.2Hz,4H),3.57(dt,J=9.3,6.7Hz,4H),3.41(dt,J=9.3,6.7Hz,4H) ,2.56-2.46(m,6H),2.32-2.24(m,4H),1.71-1.66(m,12H),1.62(m,4H),1.59-1 .54(m,10H),1.40-1.25(m,28H),1.01(t,J=7.1Hz,6H),0.89(t,J=7.0Hz,12H).

[1342] LC-MS(ESI): Calculated for 902.35, Found(M+H): 903.2

[1343] Example 31 Synthesis of amino lipid compound 2043

[1344] According to the general synthesis method, compound 2039-A5 was used to replace 383-D, and the amino lipid compound 2043 was synthesized according to the fourth step of Example 1, wherein 2039-A5 (1.2 g, 1.28 mmol) and 3-diethylamino-1-propanol (1.01 g, 7.67 mmol) were used to obtain 0.56 g of amino lipid compound 2043 with a yield of 47.02% and a purity of 90.21%.

[1345] 1H NMR (600MHz, CDCl3) δ4.67(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.4Hz,2H),4 .07(t,J=6.2Hz,4H),3.57(dt,J=9.3,6.7Hz,4H),3.41(dt,J=9.3,6.7Hz,4H),2.5 6-2.47(m,6H),2.28(t,J=7.6Hz,4H),1.86-1.78(m,4H),1.72-1.65(m,8H),1.62 -1.52(m,16H),1.37-1.24(m,30H),1.01(t,J=7.1Hz,6H),0.89(t,J=7.0Hz,12H).

[1346] LC-MS(ESI): Calculated for 930.40, Found(M+H): 931.3.

[1347] Example 32 Synthesis of amino lipid compound 2044

[1348] According to the general synthesis method, compound 2040-A5 was used to replace 383-D, and the amino lipid compound 2044 was synthesized according to the third step of Example 1, wherein 2044-A5 (0.93 g, 0.96 mmol) and 3-diethylamino-1-propanol (0.76 g, 5.76 mmol) were used to obtain 0.4 g of amino lipid compound 2044 with a yield of 43.50% and a purity of 90.45%.

[1349] 1 H NMR(600MHz, CDCl3)δ4.71-4.60(m,1H),4.48(t,J=5.1Hz,2H),4.20-4.12(m,2H), 4.08(t,J=6.0Hz,4H),3.57(dt,J=9.2,6.7Hz,4H),3.41(dt,J=9.3,6.7Hz,4H),2. 57-2.45(m,6H),2.28(t,J=7.6Hz,4H),1.93-1.84(m,4H),1.73-1.65(m,8H),1.65 -1.51(m,16H),1.35-1.25(m,34H),1.02(t,J=7.1Hz,6H),0.89(t,J=6.8Hz,12H).

[1350] LC-MS(ESI): Calculated for 958.46, Found(M+H): 959.3.

[1351] Example 33 Synthesis of amino lipid compound 2045

[1352] According to the general synthesis method, compound 2041-A5 was used to replace 383-D, and the amino lipid compound 2045 was synthesized according to the fourth step of Example 1, wherein 2045-A5 (2.5 g, 2.51 mmol) and 3-diethylamino-1-propanol (1.98 g, 15.08 mmol) were used to obtain 1.2 g of amino lipid compound 2045 with a yield of 48.46% and a purity of 90.78%.

[1353] 1 H NMR (600MHz, CDCl3) δ4.71-4.61(m,1H),4.47(t,J=5.1Hz,2H),4.16(t,J=6.5 Hz, 2H), 4.06 (t, J = 6.1 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.39 (dt, J = 9.3, 6. 7Hz,4H),2.58-2.43(m,6H),2.27(t,J=7.6Hz,4H),1.90-1.74(m,6H),1.74-1. 45(m,20H),1.42-1.16(m,40H),1.00(t,J=7.1Hz,6H),0.88(t,J=6.8Hz,12H).

[1354] LC-MS(ESI):Calculated for(M+H)986.51,Found 987.1.

[1355] Example 34 Synthesis of amino lipid compound 2061

[1356] According to the general synthesis method, compound 2061-A5 was used to replace 383-D, and the amino lipid compound 2061 was synthesized according to the fourth step of Example 1, wherein 2061-A5 (1.87 g, 1.99 mmol) and 3-diethylamino-1-propanol (1.23 g, 11.94 mmol) were used to obtain 0.942 g of amino lipid compound 2061 with a yield of 53.29% and a purity of 94.25%.

[1357] 1H-NMR (600MHz, CDCl3) δ4.70-4.63(m,1H),4.48(t,J=5.2Hz,2H),4.22(t,J=5.8Hz,2H),4.07(t,J=6.2Hz,4H),3.57(dt,J=9.2,6.7Hz,4H),3.41 (dt,J=9.2,6.7Hz,4H),2.65-2.57(m,4H),2.30(ddd,J=15.3,11.8,6.9H z,14H),1.70-1.54(m,22H),1.38-1.27(m,28H),0.89(t,J=6.9Hz,12H).

[1358] LC-MS(ESI): Calculated for 888.32, Found(M+H): 888.7.

[1359] Example 35 Synthesis of amino lipid compound 851

[1360] Step 1: Synthesize 851-A1

[1361] Reaction formula:

[1362] Experimental process:

[1363] To a 100 mL round-bottom flask, EDCI (2.8 g, 14.6 mmol), DCM (50 mL), and TEA (1.47 g, 14.6 mmol) were added sequentially. The mixture was shaken and stirred for 5 minutes, followed by the addition of DMAP (0.89 g, 7.3 mmol), BHB (4,4-bis(heptyloxy)butanol) (3.09 g, 10.22 mmol), and DTN (10-oxononadecanedioic acid) (5.00 g, 14.6 mmol). The mixture was stirred at room temperature overnight. DCM (100 mL) and water (150 mL) were added, and the mixture was extracted with stirring. The layers were separated, and the organic phase was collected, washed with 50 mL of saturated sodium chloride solution, and concentrated under reduced pressure to obtain 8.2 g of crude 851-A1. The crude product was eluted with ethyl acetate:n-heptane = 2:1 to obtain 3.36 g of 851-A1, a yield of 52.3%.

[1364] Step 2: Synthesize 851-A2

[1365] Reaction formula:

[1366] Experimental process:

[1367] To a 100 mL round-bottom flask, EDCI (1.1 g, 5.74 mmol), DCM (30 mL), and TEA (0.58 g, 5.74 mmol) were added sequentially. The mixture was shaken and stirred for 5 minutes, followed by the addition of DMAP (0.29 g, 2.39 mmol), BPB (4,4-bis(pentyloxy)butanol) (1.41 g, 5.74 mmol), and 851-A1 (3.00 g, 4.78 mmol). The mixture was stirred at room temperature overnight. DCM (100 mL) and water (150 mL) were then added, and the mixture was extracted with stirring. The organic phase was collected, washed with 50 mL of saturated sodium chloride solution, and concentrated under reduced pressure to obtain 4.8 g of crude 851-A2. This crude product was eluted with ethyl acetate:n-heptane = 1.5:1 to obtain 3.42 g of 851-A2, a yield of 83.6%.

[1368] Step 3: Synthesize 851-A3

[1369] Reaction formula:

[1370] Experimental process:

[1371] To a 250 mL single-necked flask, 851-A2 (3.00 g, 3.51 mmol) was added, dissolved in methanol (30 mL), and cooled to 0°C. Sodium borohydride (0.135 g, 3.51 mmol) was added portionwise with stirring, and the mixture was incubated for 1 h. The solvent was evaporated under reduced pressure, and water (100 mL) and DCM (100 mL) were added. The mixture was stirred and extracted, and the organic phase was collected, washed with water (50 mL), and concentrated under reduced pressure to obtain 3.1 g of crude 851-A3. The crude product was eluted with ethyl acetate:n-heptane = 1.5:1 to obtain 2.86 g of 851-A3, a yield of 95.1%.

[1372] Step 4: Synthesize 851-A4

[1373] Reaction formula:

[1374] Experimental process:

[1375] To a 50 mL single-necked round-bottom flask was added 851-A3 (2.86 g, 3.34 mmol), dissolved in DCM (30 mL), and DMAP (122 mg, 1.00 mmol) and pyridine (0.66 g, 8.35 mmol). The mixture was stirred at room temperature, and p-nitrophenyl chloroformate (1.35 g, 6.68 mmol) was added portionwise. Stirring was continued for 1 h. Water (150 mL) and DCM (100 mL) were added, and the mixture was stirred and extracted. The organic phase was collected, washed with water (80 mL), and concentrated under reduced pressure to give 5.0 g of crude 851-A4. The crude product was eluted by silica gel column chromatography with ethyl acetate:n-heptane = 1.5:1 to give 3.06 g of 851-A4, with a yield of 89.6%.

[1376] Step 5: Synthesis of amino lipid compound 851

[1377] Reaction formula:

[1378] Experimental process:

[1379] To a 50 mL single-necked round-bottom flask, 851-A4 (3.00 g, 2.93 mmol) was added, dissolved in DCM (30 mL), and DMAP (108 mg, 0.88 mmol), triethylamine (0.88 mg, 8.8 mmol), and dimethylaminopropanol (1.81 g, 17.58 mmol) were added. The mixture was stirred at room temperature for 2 days, and water (100 mL) was added. DCM (100 mL) was stirred and extracted, and the organic phase was collected. The organic phase was washed with water (80 mL) and concentrated under reduced pressure to obtain 3.6 g of crude amino lipid compound 851. The crude product was eluted by silica gel column chromatography using ethyl acetate: n-heptane = 1.5:1 to obtain 1.69 g of amino lipid compound 851, with a yield of 58.3% and a purity of 97.21%.

[1380] 1 H NMR (600MHz, CDCl3) δ4.66(m,1H),4.47(dd,J=5.3,4.5Hz,2H),4.16(t,J=6.6Hz,2H ),4.07(t,J=5.9Hz,4H),3.56(dtd,J=8.8,6.7,2.0Hz,4H),3.40(dt,J=9.2,6.7Hz,4 H),2.37-2.33(m,2H),2.27(t,J=7.6Hz,4H),2.22(s,6H),1.87-1.80(m,2H),1.68( dt,J=13.0,7.4Hz,8H),1.62-1.50(m,16H),1.35-1.24(m,44H),0.92-0.85(m,12H).

[1381] LC-MS(ESI): Calculated for 986.51, Found(M+H): 987.2.

[1382] Example 36 Synthesis of amino lipid compound 854

[1383] According to the general synthesis method, compound 854-A4 was used to replace 851-A4, and the amino lipid compound 854 was synthesized according to the fifth step method of Example 35, wherein 854-A4 (2.37 g, 2.26 mmol) and 3-dimethylamino-1-propanol (1.40 g, 13.53 mmol) were used to obtain 1.2 g of amino lipid compound 854 with a yield of 52.33% and a purity of 91.41%.

[1384] 1 H NMR(600MHz, CDCl3) δ4.66(s,1H),4.47(t,J=5.2Hz,2H),4.16(t,J=6.6Hz,2H), 4.06(t,J=6.2Hz,4H),3.55(dtd,J=8.3,6.7,1.5Hz,4H),3.39(dtd,J=7.4,6.7, 0.6Hz,4H),2.39-2.34(m,2H),2.27(t,J=7.6Hz,4H),2.22(s,6H),1.87-1.80(m ,2H),1.71-1.63(m,8H),1.62-1.48(m,16H),1.34-1.22(m,48H),0.87(m,12H).

[1385] LC-MS(ESI): Calculated for 1014.57, Found(M+H): 1015.2.

[1386] Example 37 Synthesis of amino lipid compound 856

[1387] According to the general synthesis method, compound 856-A4 was used to replace 851-A4, and the amino lipid compound 856 was synthesized according to the fifth step method of Example 35, wherein 856-A4 (1.5 g, 1.36 mmol) and 3-dimethylamino-1-propanol (0.84 g, 8.13 mmol) were used to obtain 500 mg of amino lipid compound 856 with a yield of 34.45% and a purity of 94.85%.

[1388] 1H NMR (600MHz, CDCl3) δ4.67(m,1H),4.47(t,J=5.0Hz,2H),4.17(t,J=6.6Hz ,2H),4.07(t,J=6.0Hz,4H),3.59-3.53(m,4H),3.43-3.36(m,4H),2.38-2. 32(m,2H),2.28(t,J=7.6Hz,4H),2.22(s,6H),1.86-1.80(m,2H),1.68(dd, J=18.0,8.4Hz,8H),1.61-1.49(m,16H),1.36-1.24(m,56H),0.88(m,12H).

[1389] LC-MS(ESI): Calculated for 1070.67, Found(M+H): 1071.4.

[1390] Example 38 Synthesis of amino lipid compound 861

[1391] According to the general synthesis method, compound 861-A4 was used to replace 851-A4, and the amino lipid compound 861 was synthesized according to the fifth step method of Example 35, wherein 861-A4 (1.5 g, 1.51 mmol) and 3-diethylamino-1-propanol (1.19 g, 9.06 mmol) were used to obtain 900 mg of amino lipid compound 861 with a yield of 60.48% and a purity of 94.43%.

[1392] 1 H NMR (600MHz, CDCl3) δ4.71-4.63(m,1H),4.48(t,J=5.2Hz,2H),4.17(t,J=6.5Hz,2H),4.08(t,J=6.1H z,4H),3.57(dt,J=9.2,6.7Hz,4H),3.41(dt,J=9.3,6.7Hz,4H),2.54-2.46(m,6H),2.28(t,J=7.6Hz, 4H),1.85-1.77(m,2H),1.74-1.49(m,24H),1.40-1.23(m,40H),1.01(t,J=7.1Hz,6H),0.95-0.83(m,12H).

[1393] LC-MS(ESI):Calculated for 986.51,Found(M+H):987.2.

[1394] Example 39 Synthesis of amino lipid compound 862

[1395] According to the general synthesis method, amino lipid compound 862 was synthesized according to the fifth step method of Example 35, wherein 851-A4 (2.2 g, 2.15 mmol) and 3-diethylamino-1-propanol (1.69 g, 12.91 mmol) were used to obtain 910 mg of amino lipid compound 862 with a yield of 41.69% and a purity of 93.61%.

[1396] 1 H NMR (600MHz, CDCl3) δ4.71-4.62(m,1H),4.48(t,J=4.7Hz,2H),4.17(t,J=6.5Hz,2H),4.08(t,J=5.9Hz,4H),3.57(m,4H),3.41(dt,J=9.0,6.8Hz, 4H),2.56-2.45(m,6H),2.33-2.25(m,4H),1.85-1.76(m,2H),1.74-1.49 (m,26H),1.39-1.22(m,42H),1.01(t,J=7.1Hz,6H),0.93-0.83(m,12H).

[1397] LC-MS(ESI):Calculated for 1014.57,Found(M+H):1015.3.

[1398] Example 40 Synthesis of amino lipid compound 863

[1399] According to the general synthesis method, compound 863-A4 was used to replace 851-A4, and the amino lipid compound 863 was synthesized according to the fifth step method of Example 35, wherein 863-A4 (1.81 g, 1.72 mmol) and 3-diethylamino-1-propanol (1.36 g, 10.34 mmol) were used to obtain 950 mg of amino lipid compound 863 with a yield of 52.88% and a purity of 93.08%.

[1400] 1H NMR (600MHz, CDCl3) δ4.71-4.62(m,1H),4.48(t,J=4.7Hz,2H),4.17(t,J=6.5 Hz,2H),4.08(t,J=5.7Hz,4H),3.65-3.51(m,4H),3.41(dt,J=9.0,6.8Hz,4H) ,2.60-2.44(m,6H),2.28(t,J=7.5Hz,4H),1.83-1.76(m,2H),1.74-1.50(m,2 6H),1.42-1.19(m,46H),1.01(t,J=7.1Hz,6H),0.89(dt,J=13.7,7.0Hz,12H).

[1401] LC-MS(ESI):Calculated for 1042.62,Found(M+H):1043.2.

[1402] Example 41 Synthesis of amino lipid compound 864

[1403] According to the general synthesis method, compound 864-A4 was used to replace 851-A4, and the amino lipid compound 864 was synthesized according to the fifth step method of Example 35, wherein 864-A4 (2.81 g, 2.61 mmol) and 3-diethylamino-1-propanol (2.08 g, 15.63 mmol) were used to obtain 1.2 g of amino lipid compound 864 with a yield of 42.94% and a purity of 92.67%.

[1404] 1 H NMR (400MHz, CDCl3) δ4.73-4.60 (m, 1H), 4.48 (dd, J = 5.1, 4.5Hz, 2H), 4.12 (dt, J=11.4,6.3Hz,6H),3.57(dtd,J=8.8,6.7,2.0Hz,4H),3.41(dt,J=9.2,6.7Hz,4 H),2.60-2.43(m,6H),2.28(t,J=7.6Hz,4H),1.86-1.77(m,2H),1.74-1.50(m, 24H),1.41-1.20(m,52H),1.01(t,J=7.1Hz,6H),0.90(dt,J=13.7,4.4Hz,12H).

[1405] LC-MS(ESI):Calculated for 1070.67,Found(M+H):1071.3.

[1406] Example 42 Synthesis of amino lipid compound 865

[1407] According to the general synthesis method, compound 854-A4 was used to replace 851-A4, and the amino lipid compound 865 was synthesized according to the fifth step method of Example 35, wherein 854-A4 (1.5 g, 1.43 mmol) and 3-diethylamino-1-propanol (1.12 g, 8.57 mmol) were used to obtain 0.65 g of amino lipid compound 865 with a yield of 43.60% and a purity of 96.53%.

[1408] 1 H NMR (600MHz, CDCl3) δ4.71-4.63(m,1H),4.48(t,J=5.2Hz,2H),4.17(t,J=6.5Hz,2H),4.08(t,J=6.2Hz,4H),3.57(m,4H),3.44-3.36(m,4H),2.51( td,J=7.1,3.4Hz,6H),2.28(t,J=7.6Hz,4H),1.85-1.77(m,2H),1.74-1.5 0(m,24H),1.41-1.20(m,48H),1.32(m,6H),0.89(td,J=7.0,3.5Hz,12H).

[1409] LC-MS(ESI):Calculated for 1042.62,Found(M+H):1043.3

[1410] Example 43 Synthesis of amino lipid compound 867

[1411] According to the general synthesis method, compound 856-A4 was used to replace 851-A4, and the amino lipid compound 867 was synthesized according to the fifth step method of Example 35, wherein 856-A4 (2.0 g, 1.81 mmol) and 3-diethylamino-1-propanol (1.42 g, 10.84 mmol) were used to obtain 0.60 g of amino lipid compound 867 with a yield of 30.17% and a purity of 91.94%.

[1412] 1H NMR (600MHz, CDCl3) δ4.67(m,1H),4.48(dd,J=5.3,4.7Hz,2H),4.17(t,J=6.5Hz,2H),4.08(t,J=6.0Hz,4H),3.57(m,4H),3.41(m, 4H),2.55-2.48(m,6H),2.28(t,J=7.6Hz,4H),1.86-1.50(m,28H),1.38-1.22(m,54H),1.01(t,J=7.1Hz,6H),0.91-0.85(m,12H).

[1413] LC-MS(ESI): Calculated for 1098.73, Found(M+H): 1099.3.

[1414] Example 44 Synthesis of amino lipid compound 868

[1415] According to the general synthesis method, compound 868-A4 was used to replace 851-A4, and the amino lipid compound 868 was synthesized according to the fifth step method of Example 35, wherein 868-A4 (1.0 g, 0.90 mmol) and 3-diethylamino-1-propanol (0.71 g, 5.4 mmol) were used to obtain 84 mg of amino lipid compound 868 with a yield of 8.49% and a purity of 92.68%.

[1416] 1 H NMR (600MHz, CDCl3) δ4.67(m,1H),4.48(t,J=5.3Hz,2H),4.17(t,J=6.5Hz,2H ),4.08(t,J=6.2Hz,4H),3.56(dt,J=9.1,6.7Hz,4H),3.40(dt,J=9.2,6.7Hz,4 H),2.54-2.46(m,6H),2.28(t,J=7.6Hz,4H),1.84-1.77(m,2H),1.73-1.50(m, 28H),1.37-1.23(m,52H),1.01(t,J=7.1Hz,6H),0.88(td,J=6.9,1.4Hz,12H).

[1417] LC-MS(ESI): Calculated for 1098.73, Found(M+H): 1099.4.

[1418] Example 45 Synthesis of amino lipid compound 869

[1419] According to the general...

Claims

1. An amino lipid compound having a structure of formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, in, A1, A2, and A3 are one of the following: (1) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, and A3 is C1-C5 alkylene or a bond; (2) When the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene or a bond, and A1 and A2, together with the nitrogen atom to which they are commonly attached, form a nitrogen-containing heterocyclic ring; (3) When the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is H, C1-C5 alkyl or C1-C5 heteroalkyl, A3 is C1-C5 alkylene, and A1 and A3, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocycle; (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 alkylene or C1-C5 heteroalkylene, A2 is C1-C5 alkylene or C1-C5 heteroalkylene, A3 is C1-C5 alkylene, and A1, A2 and A3, together with the nitrogen atom to which they are commonly attached, form a spirocyclic heterocycle, a fused heterocycle or a bridged heterocycle containing N; A4 is a C1-C5 alkylene group or a bond; A5, A6, A7, A8 and A 12 Each independently C1-C 18 Alkylidene, C1-C 18 heteroalkylene or bond; Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, ‐C(=O)‐, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-; Y1 is -Z3C(=O)Z4-, -N(R5)-, -Z3C(=S)Z4-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP (=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -O-, -S-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S- or -SC(=O)O-; X is C or N; R1 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z6R8, -C(R6)(OA 13 Z8R9)2、-C(R6)(SA 13 Z8R9)2 or -C(R6)(SA 13 Z8R9)(OA 13 Z8R9); R2 is H, C1-C 24 Hydrocarbon, C1-C 24 Heteroalkyl, Z7R 10 、-C(R6)(OA 14 Z9R 11 )2、-C(R6)(SA 14 Z9R 11 )2 or -C(R6)(SA 14 Z9R 11 )(OA 14 Z9R 11 ); Z3 and Z4 are each independently -O-, -N(R6)-, -S- or a bond; Z6 and Z7 are each independently -C(=O)O-, -OC(=O)-, -O-, ‐C(=O)‐, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH- or -NHS(=O)2O-; R5 is -C(=O)A9Z5A 10 、-C(=O)A 11 , H or C1-C8 hydrocarbon group; Z5 is -O- or ‐S‐; Z8 and Z9 are each independently -C(=O)O-, -OC(=O)-, -O-, ‐C(=O)‐, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ​​​​​​​ R6 are each independently H or C1-C8 hydrocarbon group; R8 and R 10 Each independently represents H, C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl; R9 and R 11 Each independently C1-C 24 Hydrocarbon or C1-C containing O or S 24 heteroalkyl; A9 is a C1-C8 alkylene group or a bond; A 10 and A 11 Each is independently a C1-C8 hydrocarbon group; A 13 and A 14 are each independently C1-C8 alkylene, C1-C8 heteroalkylene or a bond; Preferably, the hydrocarbon group is an alkyl group, an alkenyl group or an alkynyl group; Preferably, the hydrocarbylene group is an alkylene group, an alkenylene group or an alkynylene group; Preferably, the heteroalkyl group is a heteroalkyl group, a heteroalkenyl group or a heteroalkynyl group; Preferably, the heteroalkylene group is a heteroalkylene group, a heteroalkenylene group or a heteroalkynylene group.

2. The amino lipid compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, having the structure shown in formula (II-VIa):

3. The amino lipid compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, having the structure shown in formula (II-IVa):

4. The amino lipid compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, having the structure shown in formula (II-VIa-c):

5. The amino lipid compound according to any one of claims 1 and 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -Z3C(=O)Z4- or -N(R5)-.

6. The amino lipid compound according to any one of claims 1, 2 and 5, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(R6)C(=O)O-, -OC(=O)N(R6)- or -OC(=O)O-.

7. The amino lipid compound according to any one of claims 1, 2, 5 and 6, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)O-.

8. The amino lipid compound according to any one of claims 1, 2, 5 and 6, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(H)C(=O)O-.

9. The amino lipid compound according to any one of claims 1, 2, 5 and 6, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)N(H)-.

10. The amino lipid compound according to any one of claims 1, 2 and 5, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(R5)-.

11. The amino lipid compound according to any one of claims 1, 2, 5 and 10, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(C(=O)A9OA 10 )-.

12. The amino lipid compound according to any one of claims 1, 2, 5 and 10, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(C(=O)A 10 )-.

13. The amino lipid compound according to any one of claims 1, 2, 5 to 12, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are each independently -C(=O)O- or -OC(=O)-.

14. The amino lipid compound according to any one of claims 1, 2, 5 to 13, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 is -C(=O)O-.

15. The amino lipid compound according to any one of claims 1, 2, 5 to 13, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 is -OC(=O)-.

16. The amino lipid compound according to any one of claims 1, 2, 5 to 13, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z2 is -C(=O)O-.

17. The amino lipid compound according to any one of claims 1, 2, 5 to 13, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z2 is -OC(=O)-.

18. The amino lipid compound according to any one of claims 1, 2, 5 to 14, 16, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are -C(=O)O-.

19. The amino lipid compound according to any one of claims 1, 2, 5 to 13, 15 and 17, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 and Z2 are -OC(=O)-.

20. The amino lipid compound according to any one of claims 1, 2, 5 to 14 and 17, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 is -C(=O)O-, and Z2 is -OC(=O)-.

21. The amino lipid compound according to any one of claims 1, 2, 5 to 20, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(R6)(OR9)2.

22. The amino lipid compound according to any one of claims 1, 2, 5 to 21, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(H)(OR9)2.

23. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is -C(R6)(OR 11 )2.

24. The amino lipid compound according to any one of claims 1, 2, 5 to 23, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is -C(H)(OR 11 )2.

25. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 for Z7R 10 .

26. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is -C(=O)OR 10 .

27. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is -OC(=O)R 10 .

28. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is -OR 10 .

29. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is -N(H)C(=O)R 10 .

30. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is -C(=O)N(R6)R 10 .

31. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R2 is substituted C1-C 24 alkyl.

32. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(R6)(OR9)2, R2 is -C(R6)(OR 11 )2.

33. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

34. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(H)(OR9)2, R2 is -C(=O)OR 10 .

35. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(H)(OR9)2, R2 is -OC(=O)R 10 .

36. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(H)(OR9)2, R2 is -OR 10 .

37. The amino lipid compound according to any one of claims 1, 2, 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R1 is -C(H)(OR9)2, R2 is C1-C substituted by hydroxyl 24 alkyl.

38. The amino lipid compound of any one of claims 1, 2, 5 to 7, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -C(=O)OR 10 .

39. The amino lipid compound of any one of claims 1, 2, 5 to 7, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -OC(=O)R 10 .

40. The amino lipid compound of any one of claims 1, 2, 5 to 7, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -OR 10 .

41. The amino lipid compound of any one of claims 1, 2, 5 to 7, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is C1-C 24 alkyl.

42. The amino lipid compound of any one of claims 1, 2, 5 to 7, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)O-, A7 and A8 are unsubstituted C1-C5 alkylene, R1 is -C(H)(OR9)2, R2 is -C(=O)OR 10 .

43. The amino lipid compound of any one of claims 1, 2, 5 to 7, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)O-, A7 and A8 are unsubstituted C1-C5 alkylene, R1 is -C(H)(OR9)2, R2 is -OC(=O)R 10 .

44. The amino lipid compound of any one of claims 1, 2, 5, 6, 8, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(H)C(=O)O-, R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

45. The amino lipid compound of any one of claims 1, 2, 5, 6, 9, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -OC(=O)N(H)-, R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

46. ​​The amino lipid compound of any one of claims 1, 2, 5, 6, 11, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(C(=O)A9OA 10 )-, R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

47. The amino lipid compound of any one of claims 1, 2, 5, 6, 12, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(C(=O)A 10 )-, R1 is -C(H)(OR9)2, R2 is -C(H)(OR 11 )2.

48. The amino lipid compound of any one of claims 1, 2, 5, 6, 12, 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Y1 is -N(C(=O)A 10 )-, R1 is -C(H)(OR9)2, R2 is C1-C substituted by hydroxyl 24 alkyl.

49. The amino lipid compound according to any one of claims 1, 2, 5 to 48, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 9 is a C1-C5 alkylene group.

50. The amino lipid compound according to any one of claims 1, 2, 5 to 49, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 10 It is a C1-C8 alkyl group.

51. The amino lipid compound of any one of claims 1, 2, 5 to 50, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R 10 C1-C 24 Alkyl, C2-C 24 Alkenyl or C2-C 24 Alkynyl.

52. The amino lipid compound of any one of claims 1, 2, 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R 10 It is a straight-chain C2-C8 alkyl group.

53. The amino lipid compound of any one of claims 1, 2, 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R 10 For branched C7-C 18 alkyl.

54. The amino lipid compound according to any one of claims 1, 2, 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R 10 C5-C 12 Alkenyl.

55. The amino lipid compound of any one of claims 1, 2, 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R 10 C5-C 12 Alkynyl.

56. The amino lipid compound of any one of claims 1, 2, 5 to 55, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R9 is C9-C 11 Alkynyl, such as C 10 Alkynyl.

57. The amino lipid compound of any one of claims 1, 2, 5 to 56, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R 14 It is a C1-C5 alkyl group.

58. The amino lipid compound of any one of claims 1, 2, 5 to 56, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: R 14 It is a C4-C8 alkenyl group having one double bond.

59. The amino lipid compound according to any one of claims 1 and 3, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 12 It is a C2-C3 alkylene group.

60. The amino lipid compound according to any one of claims 1 and 3, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 12 A5 and A6 are each independently C3-C9 alkylene (eg, C4-C9 alkylene, C5-C9 alkylene, C6 alkylene, C7 alkylene, C8 alkylene).

61. The amino lipid compound according to any one of claims 1, 3 and 4, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -C(=O)S-, -SC(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O- or -OP(=O)(H)O-.

62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 is -C(=O)O-.

63. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 is -OC(=O)-.

64. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 is -OC(=O)O-.

65. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 is -N(H)C(=O)O-.

66. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z1 is -OC(=O)N(H)-.

67. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z2 is -C(=O)O-.

68. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z2 is -OC(=O)-.

69. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z2 is -OC(=O)O-.

70. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z2 is -N(H)C(=O)O-.

71. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z2 is -OC(=O)N(H)-.

72. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are -C(=O)O-.

73. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are -OC(=O)-.

74. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are -OC(=O)O-.

75. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are -N(H)C(=O)O-.

76. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 and Z2 are -OC(=O)N(H)-.

77. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Z 1 is -C(=O)O-, and Z2 is -OC(=O)-.

78. The amino lipid compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A4 is a key.

79. The amino lipid compound according to any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 5 and A6 are each independently C3-C 10 Alkylene.

80. The amino lipid compound according to any one of claims 1 to 79, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A A7 and A8 are each independently C2-C4 alkylene or C5-C 10 Alkylene.

81. The amino lipid compound of any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Each R9 is independently a C3-C9 alkyl group.

82. The amino lipid compound of any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Each R9 is independently C5-C8 alkenyl.

83. The amino lipid compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Each R 11 Each is independently a C3-C9 alkyl group.

84. The amino lipid compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: Each R 11 Each is independently a C5-C8 alkenyl group.

85. The amino lipid compound according to any one of claims 1 to 84, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: The dotted line between A1 and A2 and the dotted line connecting A1 and A3 do not exist.

86. The amino lipid compound according to any one of claims 1 to 84, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: The dotted line between A1 and A2 is a bond and the dotted line connecting A1 and A3 is absent.

87. The amino lipid compound according to any one of claims 1 to 84, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: The dotted line between A1 and A3 is a bond and the dotted line connecting A1 and A2 is absent.

88. The amino lipid compound according to any one of claims 1 to 87, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A A1 and A2 are each independently a C1-C5 alkyl group or a C1-C5 alkylene group.

89. The amino lipid compound of any one of claims 1 to 85 and 88, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A1 and A2 are each independently a C1-C3 alkyl group.

90. The amino lipid compound according to claim 89, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A A1 and A2 are each independently a C1-C2 alkyl group.

91. The amino lipid compound according to claim 88, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 2 is a C1-C3 alkyl group.

92. The amino lipid compound according to claim 88, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 2 is a C1-C2 alkyl group.

93. The amino lipid compound according to any one of claims 1 to 92, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 3 is a C1-C5 alkylene group.

94. The amino lipid compound according to any one of claims 1 to 93, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: A 3 is a C2-C4 alkylene group.

95. The amino lipid compound of any one of claims 1 to 84, 86, 88, 93 and 94, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: When the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 and A2 together with the nitrogen atom to which they are commonly attached form a four-membered, five-membered or six-membered heterocyclic ring containing N.

96. An amino lipid compound according to any one of claims 1 to 84, 87, 88, 91 to 94, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein: when the dotted line connecting A1 and A3 is a bond and the dotted line connecting A1 and A2 is absent, A1 and A3 together with the nitrogen atom to which they are commonly attached form a four-membered, five-membered or six-membered heterocyclic ring containing N.

97. The amino lipid compound according to any one of claims 1 to 96, having one of the structures shown below:

98. Lipid nanoparticles comprising the amino lipid compound of any one of claims 1 to 97.

99. The lipid nanoparticle of claim 98, further comprising a biologically active ingredient; Preferably, the bioactive component is a nucleic acid.

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

101. Use of the amino lipid compound of any one of claims 1 to 97 for preparing a delivery vehicle for an active ingredient; Preferably, the active ingredient is a pharmaceutical active ingredient, preferably a nucleic acid.

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

103. The use according to claim 101, wherein the medicament is used for the treatment and / or prevention of a disease; Preferably, the medicament is used for gene therapy, protein replacement therapy, antisense therapy, therapy by interfering RNA or genetic vaccination.

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

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

106. The method of claim 105, wherein the nucleic acid is selected from the group consisting of RNA, antisense oligonucleotides, and DNA; Preferably, the RNA is selected from messenger RNA (mRNA), ribosomal RNA (rRNA), microRNA (miRNA), transfer RNA (tRNA), small inhibitory RNA (siRNA), small nuclear RNA (snRNA), small hairpin RNA (shRNA), single-stranded guide RNA (sgRNA), cas9 mRNA or a mixture thereof; Preferably, the DNA is a plasmid.

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