Compounds comprising nucleic acids and half-life extending motifs

Abstract

Disclosed herein are compounds comprising a nucleic acid (A), their preparation and their uses.

Description

[0001] The applicant filed PCT application PCT / US2020 / 062358 on November 25, 2020, entitled "Compounds comprising nucleic acids and half-life-extending motifs". This PCT application entered the Chinese national phase on July 21, 2022, with application number 202080094151.1. This application is a divisional application of that Chinese application.

[0002] Cross-reference to related applications

[0003] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 940,835, filed November 26, 2019, which is incorporated herein by reference in its entirety for all purposes.

[0004] References to "sequence lists", tables, or appendices to lists of computer programs submitted as ASCII files.

[0005] The sequence list written to the file DTX-003-01WO_ST25.TXT, created on November 23, 2020, is 1,174 bytes in size, is on an IBM-PC machine, and runs on the MS Windows operating system. This is incorporated herein by reference. Technical Field

[0006] This disclosure relates to the field of bioactive compounds comprising nucleic acids. More specifically, this disclosure relates to compounds comprising nucleic acids, their preparation, and their uses. Background Technology

[0007] Delivering therapeutic nucleic acids into cells remains a challenging research area. Therefore, there is a need for improved nucleic acid compounds and strategies for introducing such compounds into cells. Summary of the Invention

[0008] This article provides, in particular, compounds or compounds containing nucleic acids (A) covalently bonded to a half-life extension motif (HLEM).

[0009] On the one hand, compounds having the following formula (I) are provided: (HLEM) z -A (I). z is an integer from 1 to 5.

[0010] In an embodiment, the half-life-extending motif has the following structure: (III). k is an integer from 1 to 5.

[0011] L 1 Independently covalent linkers. L 2 It is an unsubstituted alkylene group on its own.

[0012] In this embodiment, the nucleic acid is covalently bonded to an uptake motif (UM).

[0013] In the embodiments, the compound has formula (II): (HLEM) z -A-(UM) t (II). t is an integer from 1 to 5.

[0014] In an embodiment, the uptake motif independently has the following structure: (IV).

[0015] L 3 and L 4 Independently for the bond, -N(R) 23 )-, -O-, -S-, -C(O)-, -N(R 23 )C(O)-、-C(O)N(R 24 )-、-N(R 23 )C(O)N(R 24 -, -C(O)O-, -OC(O)-, -N(R) 23 )C(O)O-、-OC(O)N(R 24 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25 )-O-、-OP(S)(R 25 )-O-、-OP(O)(NR 23 R 24 -N-、-OP(S)(NR) 23 R 24 )-N-、-OP(O)(NR 23 R 24 )-O-、-OP(S)(NR 23 R 24 )-O-、-P(O)(NR 23 R 24 -N-、-P(S)(NR) 23 R 24 -N-、-P(O)(NR) 23 R 24 )-O-、-P(S)(NR 23 R 24 -O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. Each R 23 R 24 and R25 Independently hydrogen or unsubstituted C1-C 10 alkyl.

[0016] L 5 -L 5A -L 5B -L 5C -L 5D -L 5E -. L 6 -L 6A -L 6B -L 6C -L 6D -L 6E -. L 5A L 5B L 5C L 5D L 5E L 6A L 6B L 6C L 6D and L 6E Independently, it is a bond, -NH-, -O-, -S-, -C(O)-, -NHC(O)-, -NHC(O)NH-, -C(O)O-, -OC(O)-, -C(O)NH-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

[0017] R 1 and R 2 Independent for unsubstituted C1-C 25 Alkyl, wherein R 1 and R 2 At least one of them is unsubstituted C9-C 19 Alkyl group. R 3 It can be hydrogen, -NH2, -OH, -SH, -C(O)H, -C(O)NH2, -NHC(O)H, -NHC(O)OH, -NHC(O)NH2, -C(O)OH, -OC(O)H, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

[0018] On the one hand, a method is provided that involves contacting cells with a compound as described herein or a compound containing nucleic acid (A).

[0019] On the one hand, a method is provided that includes administering to a subject a compound as described herein or a compound containing nucleic acid (A).

[0020] On the one hand, a compound or a compound containing nucleic acid (A) is provided for use in a therapy as described herein.

[0021] On one hand, a method for introducing nucleic acids into cells within a subject is provided. The method comprises administering to the subject a compound containing nucleic acid (A) as described herein.

[0022] On the one hand, a cell comprising a compound containing nucleic acid (A) as described herein is provided.

[0023] On one hand, a pharmaceutical composition is provided comprising a pharmaceutically acceptable excipient and a compound comprising a nucleic acid (A) as described herein.

[0024] Other aspects are disclosed below. Attached Figure Description

[0025] Figure 1A The structure of DT-000137 according to an exemplary embodiment is shown.

[0026] Figure 1B The structure of DT-000146 according to an exemplary embodiment is shown.

[0027] Figure 1C The structure of DT-000347 according to an exemplary embodiment is shown.

[0028] Figure 1D The structure of DT-000155 according to an exemplary embodiment is shown.

[0029] Figure 1E The structure of DT-000156 according to an exemplary embodiment is shown.

[0030] Figure 1F The structure of DT-000157 according to an exemplary embodiment is shown.

[0031] Figure 1G The structure of DT-000272 according to an exemplary embodiment is shown.

[0032] Figure 1H The structure of DT-000273 according to an exemplary embodiment is shown.

[0033] Figure 1I The structure of DT-000274 according to an exemplary embodiment is shown.

[0034] Figure 1JThe structure of DT-000275 according to an exemplary embodiment is shown.

[0035] Figure 1K The structure of DT-000276 according to an exemplary embodiment is shown.

[0036] Figure 1L The structure of DT-000277 according to an exemplary embodiment is shown.

[0037] Figure 1M The structure of DT-000278 according to an exemplary embodiment is shown.

[0038] Figure 1N The structure of DT-000350 according to an exemplary embodiment is shown.

[0039] Figure 10 The structure of DT-000183 is shown. Detailed Implementation

[0040] definition

[0041] Unless otherwise defined, all technical terms, scientific terms, abbreviations, chemical structures, and chemical formulas used herein have the same meaning as commonly understood by one of ordinary skill in the art. The chemical structures and formulas described herein are constructed according to standard rules of chemical valence known in the field of chemistry. Unless otherwise stated, all patents, applications, published applications, and other publications cited herein are incorporated herein by reference in their entirety. Unless otherwise stated, conventional methods of mass spectrometry, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA technology, and pharmacology are employed. Furthermore, the use of the term "including" and other forms such as "include," "includes," and "included" is not restrictive. As used in this specification, whether in transitional phrases or in the text of the claims, the terms "comprise(s)" and "comprising" should be interpreted in an open-ended sense. That is, these terms should be interpreted synonymously with the phrases "having at least" or "comprising at least." When used in the context of a process, the term "comprising" means that the process includes at least the described steps, but may include additional steps. When used in the context of a compound, composition, or apparatus, the term "comprising" means that the compound, composition, or apparatus includes at least the described features or components, but may also include additional features or components.

[0042] When substituents are described by conventional chemical formulas written from left to right, the substituents equally cover chemically identical substituents produced by structures written from right to left; for example, -CH2O- is equivalent to -OCH2-.

[0043] Unless otherwise stated, the term "alkyl" itself, or as part of another substituent, means a straight (i.e., unbranched) or branched carbon chain (or carbon) or combination thereof, which may be fully saturated, monounsaturated, and / or polyunsaturated, and may contain monovalent, divalent, and polyvalent groups. Alkyl groups may contain a specified number of carbons (e.g., C1-C1). 10 (This refers to a chain with one to ten carbon atoms). An alkyl group is an uncyclic chain. Examples of saturated hydrocarbon groups include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, methyl, and homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, etc. Unsaturated alkyl groups are alkyl groups having one or more double or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotonyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and higher homologs and isomers. An alkoxy group is an alkyl group connected to the rest of the molecule via an oxygen linker (-O-). The alkyl moiety can be an alkenyl moiety. The alkyl moiety can be an alkynyl moiety. The alkyl moiety can be fully saturated. An alkenyl group may contain more than one double bond and / or one or more triple bonds in addition to one or more double bonds. An alkynyl group may contain more than one triple bond and / or one or more double bonds in addition to one or more triple bonds.

[0044] In the embodiments, the term "cycloalkyl" refers to a monocyclic, bicyclic, or polycyclic cycloalkyl ring system. In the embodiments, a monocyclic system is a cycloalkyl group containing 3 to 8 carbon atoms, wherein such a group may be saturated or unsaturated, but is not aromatic. In the embodiments, the cycloalkyl group is fully saturated. Examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. A bicyclic cycloalkyl ring system is a bridged monocyclic or fused bicyclic ring. In the embodiments, a bridged monocyclic ring contains a monocyclic cycloalkyl ring, wherein two non-adjacent carbon atoms of the monocyclic ring are connected by an alkylene bridge between one carbon atom and three additional carbon atoms (i.e., in the form of (CH2)). wThe bridging group, where w is 1, 2, or 3). Representative examples of bicyclic systems include, but are not limited to, bicyclic [3.1.1]heptane, bicyclic [2.2.1]heptane, bicyclic [2.2.2]octane, bicyclic [3.2.2]nonane, bicyclic [3.3.1]nonane, and bicyclic [4.2.1]nonane. In embodiments, the fused bicyclic cycloalkyl ring system contains a monocyclic cycloalkyl ring fused with any of the following: phenyl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocyclic, or monocyclic heteroaryl. In embodiments, the bridged or fused bicyclic cycloalkyl ring is partially connected to the parent molecule via any carbon atom contained within the monocyclic cycloalkyl ring. In embodiments, the cycloalkyl group is optionally substituted with one or both groups that are independently oxygen or thio groups. In the embodiments, the fused bicyclic cycloalkyl group is a 5- or 6-membered monocyclic cycloalkyl ring, a 5- or 6-membered monocyclic cycloalkyl group, a 5- or 6-membered monocyclic cycloalkenyl group, a 5- or 6-membered monocyclic heterocyclic group, or a 5- or 6-membered monocyclic heteroaryl group fused to a benzene ring, wherein the fused bicyclic cycloalkyl group is optionally substituted by one or both groups that are independently oxygen or thio groups. In the embodiments, the polycyclic cycloalkyl ring system is a monocyclic cycloalkyl ring (base ring) fused to any of the following: (i) a ring system selected from groups consisting of: bicyclic aromatics, bicyclic heteroaryl, bicyclic cycloalkyl, bicyclic cycloalkenyl, and bicyclic heterocyclic groups; or (ii) two other ring systems independently selected from groups consisting of: phenyl, bicyclic aromatics, monocyclic or bicyclic heteroaryl, monocyclic or bicyclic cycloalkyl, monocyclic or bicyclic cycloalkenyl, and monocyclic or bicyclic heterocyclic groups. In the embodiments, the polycyclic cycloalkyl group is partially connected to the parent molecule through any carbon atom contained within the base ring. In the embodiments, the polycyclic cycloalkyl ring system is a monocyclic cycloalkyl ring (base ring) fused with any of the following: (i) a ring system selected from groups consisting of: bicyclic aromatics, bicyclic heteroaryls, bicyclic cycloalkyl, bicyclic cycloalkenyl, and bicyclic heterocyclic groups; or (ii) two other ring systems independently selected from groups consisting of: phenyl, monocyclic heteroaryls, monocyclic cycloalkyl, monocyclic cycloalkenyl, and monocyclic heterocyclic groups. Examples of polycyclic cycloalkyl groups include, but are not limited to, tetradecahydrophenanthrenyl, perhydrophenanthiazin-1-yl, and perhydrophenoxazin-1-yl.

[0045] In the embodiments, the cycloalkyl group is a cycloalkenyl group. The term "cycloalkenyl" is used according to its common, general meaning. In the embodiments, the cycloalkenyl group is a monocyclic, bicyclic, or polycyclic cycloalkenyl ring system. In the embodiments, the monocyclic cycloalkenyl ring system is a cycloalkyl group containing 3 to 8 carbon atoms, wherein such a group is unsaturated (i.e., contains at least one cyclic carbon-carbon double bond) but is not aromatic. Examples of monocyclic cycloalkenyl ring systems include cyclopentenyl and cyclohexenyl. In the embodiments, the bicyclic cycloalkenyl ring is a bridged monocyclic or fused bicyclic ring. In the embodiments, the bridged monocyclic ring contains a monocyclic cycloalkenyl ring, wherein the two non-adjacent carbon atoms of the monocyclic ring are connected by an alkylene bridge between one carbon atom and three other carbon atoms (i.e., in the form of (CH2)). w The bridging group, where w is 1, 2, or 3). Representative examples of bicyclic cycloalkenyl groups include, but are not limited to, norbornenyl and bicyclic [2.2.2]octyl-2-enyl. In embodiments, the fused bicyclic cycloalkenyl ring system contains a monocyclic cycloalkenyl ring fused to any of phenyl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocyclic, or monocyclic heteroaryl groups. In embodiments, the bridged or fused bicyclic cycloalkenyl group is partially connected to the parent molecule via any carbon atom contained within the monocyclic cycloalkenyl ring. In embodiments, the cycloalkenyl group is optionally substituted with one or both groups that are independently oxygen or thio groups. In the embodiments, the polycyclic cycloalkenyl ring contains a monocyclic cycloalkenyl ring (base ring) fused with any of the following: (i) a ring system selected from groups consisting of: bicyclic aromatics, bicyclic heteroaryls, bicyclic cycloalkyls, bicyclic cycloalkenyls, and bicyclic heterocyclic groups; or (ii) two ring systems independently selected from groups consisting of: phenyl, bicyclic aromatics, monocyclic or bicyclic heteroaryls, monocyclic or bicyclic cycloalkyls, monocyclic or bicyclic cycloalkenyls, and monocyclic or bicyclic heterocyclic groups. In the embodiments, the polycyclic cycloalkenyl group is partially connected to the parent molecule via any carbon atom contained within the base ring. In the embodiments, the polycyclic cycloalkenyl ring contains a monocyclic cycloalkenyl ring (base ring) fused with any of the following: (i) a ring system selected from groups consisting of: bicyclic aromatic, bicyclic heteroaryl, bicyclic cycloalkyl, bicyclic cycloalkenyl, and bicyclic heterocyclic groups; or (ii) two ring systems independently selected from groups consisting of: phenyl, monocyclic heteroaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, and monocyclic heterocyclic groups.

[0046] In the embodiments, the heterocyclic alkyl group is a heterocyclic group. As used herein, the term "heterocyclic group" means monocyclic, bicyclic, or polycyclic heterocycle. A heterocyclic monocyclic heterocycle is a 3-, 4-, 5-, 6-, or 7-membered ring containing at least one heteroatom independently selected from the group consisting of O, N, and S, wherein the ring is saturated or unsaturated, but not aromatic. A 3- or 4-membered ring contains one heteroatom of a group selected from O, N, and S. A 5-membered ring may contain zero or one double bond and one, two, or three heteroatoms of a group selected from O, N, and S. A 6- or 7-membered ring contains zero, one, or two double bonds and one, two, or three heteroatoms of a group selected from O, N, and S. The heterocyclic monocyclic heterocycle is partially connected to the parent molecule via any carbon or nitrogen atom contained within the heterocyclic monocyclic heterocycle. Representative examples of heterocyclic monocyclic heterocycles include, but are not limited to, aziridine, aziridine, diaziridine, 1,3-dioxanehexyl, 1,3-dioxapentyl, 1,3-dithiopentyl, 1,3-dithiaalkyl, imidazolinyl, imidazolinyl, isothiazolinyl, isothiazolinyl, isoxazolyl, isoxazolyl, morpholinyl, oxadiazolinyl, oxadiazolyl, oxazolinyl, oxazolyl, piperazine, piperidinyl, pyranyl, pyrazolinyl, thiazolinyl, pyrrololinyl, pyrrolyl, tetrahydrofuranmethyl, tetrahydrothiophenyl, thiadiazolinyl, thiadiazolinyl, thiazolinyl, tetrahydrothiazolinyl, thiomorpholinyl, 1,1-oxothiomorpholinyl (thiomorpholinone), thiopyranyl, and trithiaalkyl. A heterocyclic bicyclic heterocycle is a monocyclic heterocycle fused with any of the following: phenyl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycle, or monocyclic heteroaryl. The heterocyclic bicyclic heterocycle is connected to the parent molecule via any carbon or nitrogen atom contained within the monocyclic heterocyclic portion of the bicyclic ring system. Representative examples of bicyclic heterocycles include, but are not limited to, 2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl, indole-1-yl, indole-2-yl, indole-3-yl, 2,3-dihydrobenzothiophene-2-yl, decahydroquinolinyl, decahydroisoquinolinyl, octahydro-1H-indoleyl, and octahydrobenzofuranyl. In embodiments, the heterocyclic group is optionally substituted with one or both groups that are independently oxygen or thio groups. In some embodiments, the bicyclic heterocyclic group is a 5- or 6-membered monocyclic heterocycle, a 5- or 6-membered monocyclic cycloalkyl, a 5- or 6-membered monocyclic cycloalkenyl, a 5- or 6-membered monocyclic heterocyclic group, or a 5- or 6-membered monocyclic heteroaryl group fused to a benzene ring, wherein the bicyclic heterocyclic group is optionally substituted by one or both groups that are independently oxygen or thio groups. The polycyclic heterocyclic ring system is a monocyclic heterocyclic ring (base ring) fused to any of the following: (i) a ring system selected from groups consisting of: bicyclic aromatics, bicyclic heteroaryl, bicyclic cycloalkyl, bicyclic cycloalkenyl, and bicyclic heterocyclic groups; or (ii) two other ring systems independently selected from groups consisting of: phenyl, bicyclic aromatics, monocyclic or bicyclic heteroaryl, monocyclic or bicyclic cycloalkyl, monocyclic or bicyclic cycloalkenyl, and monocyclic or bicyclic heterocyclic groups.The polycyclic heterocyclic group is partially connected to the parent molecule via any carbon or nitrogen atom contained within the base ring. In the embodiments, the polycyclic heterocyclic ring system is a monocyclic heterocyclic ring (base ring) fused with any of the following: (i) a ring system selected from groups consisting of: bicyclic aromatics, bicyclic heteroaryls, bicyclic cycloalkyls, bicyclic cycloalkenes, and bicyclic heterocyclic groups; or (ii) two other ring systems independently selected from groups consisting of: phenyl, monocyclic heteroaryls, monocyclic cycloalkyls, monocyclic cycloalkenes, and monocyclic heterocyclic groups. Examples of polycyclic heterocyclic groups include, but are not limited to, 10H-phenthiazin-10-yl, 9,10-dihydroacrylin-9-yl, 9,10-dihydroacrylin-10-yl, 10H-phenoxazin-10-yl, 10,11-dihydro-5H-dibenzo[b,f]azapheno-5-yl, 1,2,3,4-tetrahydropyrido[4,3-g]isoquinoline-2-yl, 12H-benzo[b]phenoxazin-12-yl, and dodecahydro-1H-carbazole-9-yl.

[0047] Unless otherwise stated, the term "alkylene" itself, or as part of another substituent, refers to a divalent group derived from an alkyl group, such as (but not limited to) those exemplified by -CH2CH2CH2CH2-. Typically, an alkyl (or alkylene) will have 1 to 24 carbon atoms, with those having 10 or fewer carbon atoms being preferred herein. "Lower alkyl" or "lower alkylene" is a short-chain alkyl or alkylene group that typically has eight or fewer carbon atoms. Unless otherwise stated, the term "alkenyl" itself, or as part of another substituent, refers to a divalent group derived from an olefin.

[0048] Unless otherwise stated, the term "heteroalkyl" on its own or in combination with another term means a stable straight or branched chain or combination thereof comprising at least one carbon atom and at least one heteroatom (e.g., O, N, S, Si, or P), wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. One or more heteroatoms (e.g., O, N, S, Si, or P) may be placed at any internal position of the heteroalkyl group or at the position where the alkyl group is attached to the rest of the molecule. Heteroalkyl groups are uncyclic chains. Examples include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2, -S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, -O-CH2-CH3, and -CN. At most two or three heteroatoms can be consecutive, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. The heteroalkyl moiety may contain one heteroatom (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain two optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain three optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain four optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain five optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain up to eight optionally different heteroatoms (e.g., O, N, S, Si, or P). Unless otherwise stated, the term "heteroalkenyl" itself, or in combination with another term, means a heteroalkyl group containing at least one double bond. A heteroalkenyl group may optionally contain more than one double bond and / or one or more triple bonds in addition to one or more double bonds. Unless otherwise stated, the term "heteroyynyl" itself, or in combination with another term, means a heteroalkyl group containing at least one triple bond. A heteroyynyl group may optionally contain more than one triple bond and / or one or more double bonds in addition to one or more triple bonds.

[0049] Similarly, unless otherwise stated, the term "heteroalkylene" itself, or as part of another substituent, refers to a divalent group derived from a heteroalkylene group, such as (but not limited to) those exemplified by -CH2-CH2-S-CH2-CH2- and -CH2-S-CH2-CH2-NH-CH2-. For heteroalkylene groups, the heteroatom may also occupy any one or both of the chain ends (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Furthermore, for alkylene and heteroalkyl linking groups, the direction in which the formula of the linking group is written does not imply the orientation of the linking group. For example, the formula -C(O)2R'- represents both -C(O)2R'- and -R'C(O)2-. As described above, heteroalkyl groups as used herein include those groups connected to the remainder of the molecule via heteroatoms, such as -C(O)R', -C(O)NR', ​​-NR'R", -OR', -SR', and / or -SO2R'. It should be understood that the terms "heteroalkyl" and "-NR'R" are not redundant or mutually exclusive when a specific heteroalkyl group is described following a description of such a group. Rather, the specific heteroalkyl group is described for clarity. Therefore, the term "heteroalkyl" should not be construed herein as excluding specific heteroalkyl groups such as "-NR'R".

[0050] Unless otherwise stated, the terms "cycloalkyl" and "heterocycloalkyl" on their own or in combination with other terms refer to the cyclic form of "alkyl" and "heteroalkyl," respectively. Cycloalkyl and heterocycloalkyl are not aromatic. Additionally, for heterocycloalkyl, the heteroatom may occupy the position where the heterocycle is attached to the rest of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, etc. Examples of heterocycloalkyl include, but are not limited to, 1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothiophen-2-yl, tetrahydrothiophen-3-yl, 1-piperazinyl, 2-piperazinyl, etc. "Cycloalkylene" and "heterocyclic alkylene" refer, alone or as part of another substituent, to divalent groups derived from cycloalkylene and heterocyclic alkylene, respectively.

[0051] Unless otherwise stated, the term "halogen" or "halogen" itself, or as part of another substituent, refers to a fluorine, chlorine, bromine, or iodine atom. Additionally, terms such as "haloalkyl" refer to alkyl groups containing both monohaloalkyl and polyhaloalkyl groups. For example, the term "halo(C1-C4)alkyl" includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, etc.

[0052] Unless otherwise stated, the term "acyl" means -C(O)R, where R is a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0053] Unless otherwise stated, the term "aryl" refers to a polyunsaturated aromatic hydrocarbon substituent, which may be a monocyclic or fused together (i.e., a fused-ring aryl) or a plurality of covalently linked rings (preferably 1 to 3 rings). A fused-ring aryl refers to a plurality of fused rings, wherein at least one of the fused rings is an aryl ring. The term "heteroaryl" refers to an aryl (or ring) containing at least one heteroatom (such as N, O, or S), wherein the nitrogen and sulfur atoms are optionally oxidized, and one or more nitrogen atoms are optionally quaternized. Thus, the term "heteroaryl" encompasses fused-ring heteroaryl (i.e., a plurality of fused rings, wherein at least one of the fused rings is a heteroaryl ring). 5,6-fused-ring heteroaryl refers to two rings fused together, one ring having 5 members and the other ring having 6 members, and at least one ring being a heteroaryl ring. Similarly, 6,6-fused-ring heteroaryl refers to two rings fused together, one ring having 6 members and the other ring having 6 members, and at least one ring being a heteroaryl ring. Furthermore, 6,5-fused-ring heteroaryl refers to two fused rings, one with 6 members and the other with 5 members, and at least one of the rings is a heteroaryl ring. The heteroaryl group can be attached to the rest of the molecule via a carbon atom or a heteroatom. Non-limiting examples of aryl and heteroaryl groups include phenyl, naphthyl, pyrrolyl, pyrazolyl, pyridazinyl, triazinyl, pyrimidinyl, imidazolyl, pyrazinyl, purinyl, oxazolyl, isoxazolyl, thiazolyl, furanyl, thiopheneyl, pyridinyl, pyrimidinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzofuran, isobenzofuranyl, indolyl, isoindolyl, benzothiaphenyl, isoquinolinyl, quinoxalinyl, quinolinyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl. The following are substituents: pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isooxazolyl, 4-isooxazolyl, 5-isooxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-benzothiazolyl, purinel, 2-benzimidazolyl, 5-indolyl, 1-isoquinolinyl, 5-isoquinolinyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolinyl, and 6-quinolinyl. The substituents in each of the aryl and heteroaryl ring systems indicated above are selected from the group of acceptable substituents described below. Alone or as part of another substituent, "arylene" and "heteroarylene" refer to divalent groups derived from aryl and heteroaryl groups, respectively. Heteroaryl substituents can be -O- bonded to a nitrogen atom in a cyclic heteroatom.

[0054] A spirocycle is a group of two or more rings in which adjacent rings are connected by a single atom. Individual rings within a spirocycle can be the same or different. Individual rings within a spirocycle can be substituted or unsubstituted and can have substituents different from those of other individual rings in the spirocycle group. Possible substituents of individual rings within a spirocycle are possible substituents of the same ring when not part of the spirocycle (e.g., substituents of cycloalkyl or heteroalkyl rings). A spirocycle can be a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkylene, a substituted or unsubstituted heteroalkyl, or a substituted or unsubstituted heteroalkylene, and the individual ring within the spirocycle group can be any ring in the immediately preceding list, encompassing all rings of one type (e.g., all rings of substituted heteroalkylene, where each ring can be the same or different substituted heteroalkylene). When referring to spirocycle systems, heterocyclic spirocycles mean spirocycles in which at least one ring is a heterocycle and where each ring can be a different ring. When referring to spirocyclic systems, a substituted spirocyclic system means that at least one ring is substituted and each substituent may optionally be different.

[0055] symbol" "" indicates the point where the chemical part connects to the rest of the molecule or chemical formula.

[0056] As used herein, the term "oxygen group (oxo)" refers to oxygen that is double-bonded to a carbon atom.

[0057] The term "alkylarylene" refers to an arylene moiety covalently bonded to an alkylene moiety (also referred to herein as an alkylene linker). In the embodiments, the alkylarylene has the following formula: or .

[0058] The alkylarylene moiety may be substituted (e.g., with substituents) at the alkylene moiety or the arylene linker (e.g., at carbon 2, 3, 4, or 6) with the following: halogen, oxy, -N3, -CF3, -CCl3, -CBr3, -CI3, -CN, -CHO, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO2CH3, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, substituted or unsubstituted C1-C5 alkyl or substituted or unsubstituted 2- to 5-membered heteroalkyl. In the examples, the alkylarylene is unsubstituted.

[0059] Each of the above terms (e.g., "alkyl", "heteroalkyl", "cycloalkyl", "heterocycloalkyl", "aryl", and "heteroaryl") includes both substituted and unsubstituted forms of the indicated group. Preferred substituents for each type of group are provided below.

[0060] The substituents of alkyl and heteroalkyl groups (including those commonly referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, ynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) may be one or more selected from, but not limited to, the following groups: -OR', =O, =NR', =N-OR', -NR'R", -SR', halogen, -SiR'R"R"', -OC(O)R', -C(O)R', -CO2R', -CONR'R"', -OC(O)N R'R", -NR"C(O)R', -NR'-C(O)NR"R"', -NR"C(O)2R', -NR-C(NR'R"R"')=NR"", -NR-C(NR'R")=NR"', -S (O)R', -S(O)2R', -S(O)2NR'R", -NRSO2R', -NR'NR"R"', -ONR'R", -NR'C(O)NR"NR"'R"", -CN, -NO2, -N R'SO2R", -NR'C(O)R", -NR'C(O)-OR", -NR'OR", the number of which is in the range of zero to (2m'+1), where m' is the total number of carbon atoms in such groups. R, R', R", R"' and R"" each preferably independently refer to hydrogen, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, or a substituted or unsubstituted aryl (e.g., substituted with 1-3 halogens). The R group comprises aryl groups, substituted or unsubstituted heteroaryl groups, substituted or unsubstituted alkyl groups, alkoxy or thioalkoxy or aralkyl groups. When the compounds described herein contain more than one R group, each of the R groups is selected independently, for example, as if each R' group, R" group, R"' group and R"" group were selected independently when more than one of these groups were present. When R' and R" are attached to the same nitrogen atom, they can combine with said nitrogen atom to form a 4-membered, 5-membered, 6-membered or 7-membered ring. For example, -NR'R" contains, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl. Based on the above discussion of substituents, those skilled in the art will understand that the term "alkyl" is intended to include groups containing a carbon atom bonded to a group other than a hydrogen group, such as haloalkyl (e.g., -CF3 and -CH2CF3) and acyl (e.g., -C(O)CH3, -C(O)CF3, -C(O)CH2OCH3, etc.).

[0061] Similar to the substituents described for alkyl groups, the substituents for aryl and heteroaryl groups are varied and selected from, for example, the following: -OR', -NR'R", -SR', halogen, -SiR'R"R"', -OC(O)R', -C(O)R', -CO2R', -CONR'R"', -OC(O)NR'R"', -NR"C(O)R', -NR'-C(O)NR"R"', -NR"C(O)2R, -NR-C(NR'R"R"')=NR"', -NR-C(NR'R")=NR"', -S(O)R', -S(O)2R', -S(O)2NR'R"', -NRSO2R, -NR'NR"R"', -ONR'R"', -NR'C(O)NR"NR"'R"', -CN, -NO2, -R', -N3, - CH(Ph)2, fluoro(C1-C4)alkoxy and fluoro(C1-C4)alkyl, -NR'SO2R", -NR'C(O)R", -NR'C(O)-OR", -NR'OR", the number of which is in the range from zero to the total number of open valences on the aromatic ring system; and wherein R', R", R"' and R"" are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. When the compound described herein contains more than one R group, each of the R groups is selected independently, for example, as if each R' group, R" group, R"' group and R"" group were selected independently when more than one of these groups were present.

[0062] Substituents on a ring (e.g., cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene) can be described as substituents on the ring rather than on a specific atom of the ring (often referred to as floating substituents). In this case, the substituent can be attached to any ring atom (following the valence rules), and in the case of fused or spirocyclic rings, the substituent described as associated with one member of the fused or spirocyclic ring (floating substituents on a single ring) can be a substituent on any of the fused or spirocyclic rings (floating substituents on multiple rings). When the substituent is attached to the ring rather than a specific atom (floating substituent) and the substituent's subscript is an integer greater than one, multiple substituents can be located on the same atom, the same ring, different atoms, different fused rings, or different spirocyclic rings, and each substituent can optionally be different. Where the connection point between the ring and the rest of the molecule is not limited to a single atom (floating substituent), the connection point can be any atom of the ring, and in the case of fused or spirocyclic rings, it can be any atom of any of the fused or spirocyclic rings (following the valence rules). In the case where a ring, fused ring, or spirocyclic ring contains one or more cyclic heteroatoms and the ring, fused ring, or spirocyclic ring is shown having another floating substituent (including, but not limited to, a connection point with the rest of the molecule), the floating substituent may be bonded to the heteroatom. In the case where the cyclic heteroatom is shown bonded to one or more hydrogen atoms in a structure or formula having a floating substituent (e.g., a cyclic nitrogen having two bonds connected to a ring atom and a third bond connected to a hydrogen atom), when the heteroatom is bonded to the floating substituent, the substituent will be understood as replacing the hydrogen while following the rules of chemical valence.

[0063] Two or more substituents may be optionally linked to form aryl, heteroaryl, cycloalkyl, or heterocycloalkyl groups. Such so-called ring-forming substituents are typically (though not mandatory) linked to a cyclic base structure. In one embodiment, the ring-forming substituent is linked to an adjacent member of the base structure. For example, two ring-forming substituents linked to an adjacent member of the cyclic base structure produce a fused-ring structure. In another embodiment, the ring-forming substituent is linked to a single member of the base structure. For example, two ring-forming substituents linked to a single member of the cyclic base structure produce a spirocyclic structure. In yet another embodiment, the ring-forming substituent is linked to a non-adjacent member of the base structure.

[0064] The two substituents on adjacent atoms of the aryl or heteroaryl ring can optionally form the general formula -TC(O)-(CRR'). q A -U- ring, where T and U are independently -NR-, -O-, -CRR'-, or single bonds, and q is an integer from 0 to 3. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be of the formula -A-(CH2). rThe substituents of -B- are used, where A and B are independently -CRR'-, -O-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)2NR'-, or single bonds, and r is an integer from 1 to 4. One of the single bonds in the newly formed ring may optionally be replaced by a double bond. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be of the formula -(CRR'). s -X'-(C"R"R"') d The substituents are substituted, wherein s and d are independently integers from 0 to 3, and X' is -O-, -NR'-, -S-, -S(O)-, -S(O)2-, or -S(O)2NR'-. The substituents R, R', R" and R"' are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl.

[0065] As used herein, the term “heteroatom” or “cyclic heteroatom” means that it contains oxygen (O), nitrogen (N), sulfur (S), phosphorus (P) and silicon (Si).

[0066] As used herein, "substituent" means a group selected from the following: (A) Oxygen group, halogen, -CF3, -CCl3, -CBr3, -CI3, -CHF2, -CHCl2, -CHBr2, -CHI2, -CH2F, -CH2Cl, -CH2Br, -CH2I, -CN, -N3, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, NHNH2, ONH2, NHC(O)NHNH2、 NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCl3, -OCBr3, -OCI3, -OCHF2, -OCHCl2, -OCHBr2, -OCHI2, -OCH2F, -OCH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl groups (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl groups (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted cycloalkyl groups (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl, or 5- to 6-membered heterocycloalkyl), unsubstituted aryl groups (e.g., C6-C... 10 Aryl, C 10 Aryl or phenyl) or unsubstituted heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl), and (B) An alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group substituted with at least one of the following substituents: (i) Oxygen group, halogen, -CF3, -CCl3, -CBr3, -CI3, -CHF2, -CHCl2, -CHBr2, -CHI2, -CH2F, -CH2Cl, -CH2Br, -CH2I, -CN, -N3, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, NHNH2, ONH2, NHC(O)NHNH2、 NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCl3, -OCBr3, -OCI3, -OCHF2, -OCHCl2, -OCHBr2, -OCHI2, -OCH2F, -OCH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl groups (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl groups (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted cycloalkyl groups (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl, or 5- to 6-membered heterocycloalkyl), unsubstituted aryl groups (e.g., C6-C... 10 Aryl, C 10Aryl or phenyl) or unsubstituted heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl), and (ii) An alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group substituted with at least one of the following substituents: (a) Oxygen group, halogen, -CF3, -CCl3, -CBr3, -CI3, -CHF2, -CHCl2, -CHBr2, -CHI2, -CH2F, -CH2Cl, -CH2Br, -CH2I, -CN, -N3, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, NHNH2, ONH2, NHC(O)NHNH2、 NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCl3, -OCBr3, -OCI3, -OCHF2, -OCHCl2, -OCHBr2, -OCHI2, -OCH2F, -OCH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl groups (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl groups (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted cycloalkyl groups (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl, or 5- to 6-membered heterocycloalkyl), unsubstituted aryl groups (e.g., C6-C... 10 Aryl, C 10 Aryl or phenyl) or unsubstituted heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl), and (b) Alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl: oxy, halogen, -CF3, -CCl3, -CBr3, -CI3, -CHF2, -CHCl2, -CHBr2, -CHI2, -CH2F, -CH2Cl, -CH2Br, -CH2I, -CN, -N3, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, NHNH2, ONH2, NHC(O)NHNH2、 NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCl3, -OCBr3, -OCI3, -OCHF2, -OCHCl2, -OCHBr2, -OCHI 2、 -OCH2F, -OCH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl groups (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl groups (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted cycloalkyl groups (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl, or 5- to 6-membered heterocycloalkyl), unsubstituted aryl groups (e.g., C6-C...). 10 Aryl, C 10 (aryl or phenyl) or unsubstituted heteroaryl (e.g., 5 to 10-membered heteroaryl, 5 to 9-membered heteroaryl or 5 to 6-membered heteroaryl).

[0067] As used herein, “size-limited substituent (size-limited substituent group)” refers to a group selected from all the substituents described above for “substituents”, wherein each substituted or unsubstituted alkyl group is a substituted or unsubstituted C1-C. 20 Alkyl groups, each substituted or unsubstituted heteroalkyl group being a substituted or unsubstituted 2- to 20-membered heteroalkyl group, each substituted or unsubstituted cycloalkyl group being a substituted or unsubstituted C3-C8 cycloalkyl group, each substituted or unsubstituted heterocycloalkyl group being a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group, and each substituted or unsubstituted aryl group being a substituted or unsubstituted C6-C8 cycloalkyl group. 10 Aryl group, and each substituted or unsubstituted heteroaryl group is a substituted or unsubstituted 5 to 10-membered heteroaryl group.

[0068] As used herein, "lower substituent" refers to a group selected from all the substituents described above for "substituent," wherein each substituted or unsubstituted alkyl group is a substituted or unsubstituted C1-C8 alkyl group, each substituted or unsubstituted heteroalkyl group is a substituted or unsubstituted 2- to 8-membered heteroalkyl group, each substituted or unsubstituted cycloalkyl group is a substituted or unsubstituted C3-C7 cycloalkyl group, each substituted or unsubstituted heterocycloalkyl group is a substituted or unsubstituted 3- to 7-membered heterocycloalkyl group, and each substituted or unsubstituted aryl group is a substituted or unsubstituted C6-C8 cycloalkyl group. 10 Aryl group, and each substituted or unsubstituted heteroaryl group is a substituted or unsubstituted 5 to 9-membered heteroaryl group.

[0069] In the embodiments, the substituted or unsubstituted portions (e.g., substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene and / or substituted or unsubstituted heteroaryl) are unsubstituted (e.g., unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted alkylene, unsubstituted heteroalkylene, unsubstituted cycloalkylene, unsubstituted heterocycloalkylene, unsubstituted arylene and / or unsubstituted heteroalkylene). In the embodiments, the substituted or unsubstituted portions (e.g., substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene and / or substituted or unsubstituted heteroaryl) are substituted (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene and / or substituted heteroaryl).

[0070] In the embodiments, the substituted portion (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one substituent, wherein if the substituted portion is substituted with multiple substituents, each substituent may optionally be different. In the embodiments, if the substituted portion is substituted with multiple substituents, each substituent is different.

[0071] In embodiments, the substituted portion (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one size-restricted substituent, wherein if the substituted portion is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, if the substituted portion is substituted with multiple size-restricted substituents, each size-restricted substituent is different.

[0072] In embodiments, the substituted portion (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one lower substituent, wherein if the substituted portion is substituted with multiple lower substituents, each lower substituent may optionally be different. In embodiments, if the substituted portion is substituted with multiple lower substituents, each lower substituent is different.

[0073] In embodiments, the substituted portion (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted portion is substituted with a plurality of groups selected from substituents, size-restricted substituents, and lower substituents, each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In embodiments, if the substituted portion is substituted with a plurality of groups selected from substituents, size-restricted substituents, and lower substituents, each substituent, size-restricted substituent, and / or lower substituent is different.

[0074] In the embodiments of the compounds herein, each substituted or unsubstituted alkyl group may be substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C1-C. 20 Alkyl groups, each substituted or unsubstituted heteroalkyl group being a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 2- to 20-membered heteroalkyl group; each substituted or unsubstituted cycloalkyl group being a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C3-C8 cycloalkyl group; each substituted or unsubstituted heteroalkyl group being a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 3- to 8-membered heteroalkyl group; each substituted or unsubstituted aryl group being a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C6-C... 10 The aryl group and / or each substituted or unsubstituted heteroaryl group is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 5- to 10-membered heteroaryl group. In the embodiments herein, each substituted or unsubstituted alkylene group is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C1-C group. 20 Alkylenes, each substituted or unsubstituted heteroalkylene is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 2- to 20-membered heteroalkylene; each substituted or unsubstituted cycloalkylene is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C3-C8 cycloalkylene; each substituted or unsubstituted heteroalkylene is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 3- to 8-membered heteroalkylene; each substituted or unsubstituted arylene is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C6-C... 10 The arylene and / or each substituted or unsubstituted heteroarylene is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 5 to 10 heteroarylene groups.

[0075] In the embodiments, each substituted or unsubstituted alkyl group is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C1-C8 alkyl group; each substituted or unsubstituted heteroalkyl group is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 2- to 8-membered heteroalkyl group; each substituted or unsubstituted cycloalkyl group is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C3-C7 cycloalkyl group; each substituted or unsubstituted heterocycloalkyl group is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 3- to 7-membered heterocycloalkyl group; and each substituted or unsubstituted aryl group is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C6-C8 alkyl group. 10 The aryl group and / or each substituted or unsubstituted heteroaryl group is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 5 to 9-membered heteroaryl group. In the embodiments, each substituted or unsubstituted alkylene group is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C1-C8 alkylene group; each substituted or unsubstituted heteroalkylene group is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 2- to 8-membered heteroalkylene group; each substituted or unsubstituted cycloalkylene group is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C3-C7 cycloalkylene group; each substituted or unsubstituted heteroalkylene group is a substituted or unsubstituted 3- to 7-membered heteroalkylene group; and each substituted or unsubstituted aryl group is a substituted (e.g., substituted with a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted C6-C7 cycloalkylene group. 10 The arylene and / or each substituted or unsubstituted heteroarylene is a substituted (e.g., substituted by a substituent, a size-restricted substituent, or a lower substituent) or unsubstituted 5 to 9-membered heteroarylene. In the examples, the compounds are chemical species illustrated in the following examples section, figures, or tables.

[0076] Some of the compounds described herein have asymmetric carbon atoms (optical or chiral centers) or double bonds; enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisomers, and individual isomers of amino acids, which can be defined according to absolute stereochemistry as (R)-, (S)-, (D)-, or (L)-, are all covered within the scope of this disclosure. The compounds described herein do not include compounds known in the art that are too unstable to be synthesized and / or isolated. The compounds described herein include compounds in racemic and optically pure forms. Optically active (R)- and (S)- or (D)- and (L)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. When the compounds described herein contain olefinic bonds or other geometrically asymmetric centers, and unless otherwise specified, it is intended that these compounds contain both E and Z geometric isomers.

[0077] As used herein, the term "isomer" refers to a compound having the same number and type of atoms and therefore the same molecular weight but differing in the structural arrangement or configuration of the atoms.

[0078] As used in this paper, the term "tautomer" refers to one of two or more structural isomers that exist in equilibrium and are readily transformed from one isomer to another.

[0079] It will be apparent to those skilled in the art that some of the compounds described herein may exist in tautomeric forms, and all such tautomeric forms of the compounds are within the scope of this disclosure.

[0080] Where the compounds disclosed herein have at least one chiral center, the compounds may exist as individual enantiomers and diastereomers or as mixtures of these isomers comprising racemates. The isolation of individual isomers or the selective synthesis of individual isomers is accomplished by applying various methods well known to those skilled in the art. Unless otherwise indicated, all such isomers and mixtures thereof are included within the scope of the compounds disclosed herein. Unless otherwise stated, the structures described herein are also intended to encompass all stereochemical forms of the structures; that is, each asymmetric center… (R) Configuration and (S) Configuration. Therefore, those skilled in the art generally consider that stable single stereochemical isomers of the compounds of the present invention, as well as mixtures of enantiomers and diastereomers, are all within the scope of this disclosure.

[0081] Unless otherwise stated, the structures described herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds in which hydrogen is replaced by deuterium or tritium, or compounds in which hydrogen is enriched by deuterium or tritium, are also included. 18F replaces fluoride or is derived from 13 C or 14 Compounds having the structure of this invention, other than carbon-enriched carbon substitutes, are within the scope of this disclosure.

[0082] The compounds described herein may also contain atomic isotopes in non-natural proportions at one or more atoms constituting such compounds. For example, the compounds may contain, for instance, tritium ( 3 H), Iodine-125 ( 125 I) or carbon-14 ( 14 C) Radiolabeling with radioactive isotopes. All isotopic variations of the compounds provided herein, whether radioactive or non-radioactive, are included in this disclosure.

[0083] It should be noted that throughout the application, alternatives are written in the Markush group, for example, at each amino acid position containing more than one possible amino acid. It is specifically contemplated that each member of the Markush group should be considered individually, thereby including another embodiment, and the Markush group should not be understood as a single unit.

[0084] "Analog" or "analogue" is used according to its common, general meaning in chemistry and biology, and refers to a compound that is structurally similar but compositionally different from another compound (i.e., the so-called "reference" compound) for example, in the substitution of one atom with an atom of a different element, or in the presence of a particular functional group, or in the substitution of one functional group with another functional group, or in the absolute stereochemistry of one or more chiral centers of a reference compound. Therefore, an analog is a compound that is similar or equivalent to a reference compound in function and appearance, but dissimilar or not equivalent in structure or origin.

[0085] As used herein, the term “a / an” means one or more. Additionally, as used herein, the phrase “replaced by [n]…” means that the specified group can be replaced by one or more of any or all of the substituents in the designated substituent. For example, when a group such as an alkyl or heteroaryl is “replaced by an unsubstituted C1-C…” 20 When alkyl or unsubstituted 2 to 20 heteroalkyl groups are substituted, the group may contain one or more unsubstituted C1-C1 groups. 20 Alkyl groups, and / or one or more unsubstituted 2 to 20 heteroalkyl groups.

[0086] When a group is partially substituted by an R substituent, it can be referred to as "R-substituted". In the case of partial R substitution, the portion is substituted by at least one R substituent, and each R substituent is optionally different. When a particular R group is present in the description of a chemical genus (such as formula (I)), each appearance of that particular R group can be distinguished using Roman numerals. For example, in the presence of multiple R groups... 13 In the case of substituents, each R 13 Substituents can be classified as R 13.1 R 13.2 R 13.3 R 13.4 etc., where R 13.1 R 13.2 R 13.3 R 13.4 Each of them is in R 13 Defined within the scope of and optionally different. As used herein, the term "a / an" means one or more. Additionally, as used herein, the phrase "substituted by [n]..." means that the specified group can be substituted by one or more of any or all of the substituents of the designated substituent. For example, when a group such as an alkyl or heteroaryl is "substituted by an unsubstituted C1-C..." 20 When alkyl or unsubstituted 2 to 20 heteroalkyl groups are substituted, the group may contain one or more unsubstituted C1-C1 groups. 20 Alkyl groups, and / or one or more unsubstituted 2 to 20 heteroalkyl groups.

[0087] The descriptions of the compounds provided herein are limited by principles of chemical bonding known to those skilled in the art. Therefore, where a group can be substituted with one or more of a plurality of substituents, such substitutions are chosen to conform to the principles of chemical bonding and to obtain compounds that are not inherently unstable and / or, as known to those skilled in the art, may be unstable under environmental conditions (e.g., aqueous, neutral, and several known physiological conditions). For example, heterocyclic alkyl or heteroaryl groups, according to principles of chemical bonding known to those skilled in the art, are linked to the rest of the molecule via cyclic heteroatoms, thereby avoiding inherently unstable compounds.

[0088] The term "pharmaceutically acceptable salt" refers to a salt that retains the bioavailability and properties of a compound that is not biologically or otherwise undesirable for pharmaceutical use. In many cases, the compounds described herein are capable of forming acid and / or base salts due to the presence of amino and / or carboxyl groups or similar groups. Pharmaceutically acceptable acid addition salts can be formed from inorganic and organic acids. Inorganic acids that can be derivatized include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. Organic acids that can be derivatized include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, etc. Pharmaceutically acceptable base addition salts can be formed from inorganic and organic bases. Inorganic bases that can be derivatized include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, etc.; particularly preferred are ammonium salts, potassium salts, sodium salts, calcium salts, and magnesium salts. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, etc., specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. Many such salts are known in the art, as described in WO 87 / 05297 by Johnston et al., published on September 11, 1987 (the document is incorporated herein by reference in its entirety).

[0089] "Contact" is used in its simple, common sense, and refers to a process that allows at least two different species (e.g., chemical compounds, biomolecules, or cells) to come close enough to react, interact, or physically touch. For example, contact includes the process of bringing a compound close enough to a cell to bind to cell surface receptors.

[0090] As used herein, “cell contact” refers to a situation where a compound or other composition of substances comes into direct contact with or is close enough to cells to induce a desired biological effect in the cells.

[0091] As defined herein, the term "inhibition (inhibit / inhibiting, etc.)" means a negative effect (e.g., a reduction) on activity or function relative to the absence of an inhibitor. In embodiments, inhibition means a negative effect (e.g., a reduction) on the concentration or level of a biomolecule, such as a protein or mRNA, relative to the absence of an inhibitor. For example, inhibition includes reducing the level of mRNA expression in cells. In embodiments, inhibition refers to a reduction in the activity of a specific biomolecular target, such as a protein target or an mRNA target. Therefore, inhibition at least partially includes partially or completely blocking stimulation, reducing, preventing or delaying activation, desensitizing, or downregulating the amount of signal transduction or enzyme activity or biomolecule. In embodiments, inhibition refers to a reduction in the activity of a target biomolecule caused by a direct interaction (e.g., the inhibitor binding to a target protein). In embodiments, inhibition refers to a reduction in the activity of a target biomolecule caused by an indirect interaction (e.g., the inhibitor binding to a protein that activates the target protein, thereby preventing the target protein from activating).

[0092] The term "inhibitor" refers to a compound, composition, or substance that can detectably reduce the expression or activity of a given gene or protein. For example, an inhibitor can reduce expression or activity by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more compared to a control in the absence of an inhibitor. Inhibitors contain, for example, synthetic or biological molecules such as oligonucleotides.

[0093] As used herein, the terms “expression” and “gene expression” refer to the steps involved in translating nucleic acids into proteins, including mRNA expression and protein expression. Expression can be detected using conventional techniques used to detect nucleic acids or proteins, such as PCR, ELISA, Southern blotting, Western blotting, flow cytometry, FISH, immunofluorescence, and immunohistochemistry.

[0094] "Effective amount" is the amount of a compound sufficient, relative to the absence of the compound, to achieve its stated purpose (e.g., to achieve the effect it is applied for, to treat a disease, to reduce enzyme activity, to increase enzyme activity, to reduce signal transduction pathways, or to reduce one or more symptoms of a disease or condition). As used herein, "activity-reducing amount" refers to the amount of antagonist required to reduce enzyme activity, relative to the absence of an antagonist. As used herein, "functionally disruptive amount" refers to the amount of antagonist required to disrupt the function of an enzyme or protein, relative to the absence of an antagonist.

[0095] The term “in vivo” as used in this article refers to processes that occur within the body of the subject.

[0096] As used herein, the term "subject" refers to a human or non-human animal selected for treatment or therapy. In this embodiment, the subject is a human.

[0097] As used herein, the term "ex vivo" means a process that occurs in vitro in isolated tissues or cells, wherein the processed tissues or cells include primary cells. As is known in the art, any media used in this process can be aqueous and non-toxic, thus ensuring that the tissues or cells do not become unviable. In embodiments, the ex vivo process occurs in vitro using primary cells.

[0098] The term “application” means the provision of a medicine or composition to a subject and includes application performed by a medical professional and self-application.

[0099] The term "therapy" refers to one or more specific procedures applied to improve at least one indicator or disease or symptom. In an embodiment, the specific procedure is the administration of one or more agents.

[0100] The term "modulation" is used herein in its ordinary sense as understood by one of ordinary skill in the art, and therefore refers to the act of altering or changing one or more properties. For example, in the context of the effect of a modulator on a target molecule, modulation means altering by increasing or decreasing a property or function of the target molecule or by changing the amount of the target molecule. Modulators of diseases reduce the symptoms, causes, or characteristics of a targeted disease.

[0101] The term "nucleic acid" refers to a compound containing at least two nucleotide monomers covalently linked together. Nucleic acids include polynucleotides and oligonucleotides, wherein oligonucleotides include double-stranded oligonucleotides and single-stranded oligonucleotides and their modified versions.

[0102] The term "polynucleotide" refers to a relatively long nucleic acid, for example, one with a length of 200, 300, 500, 1000, 2000, 3000, 5000, 7000, or 10,000 nucleotides. Non-limiting examples of polynucleotides include genes, gene fragments, exons, introns, intergenic DNA (including but not limited to heterochromatic DNA), messenger RNA (mRNA), long non-coding DNA, transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched-chain polynucleotides, plasmids, vectors, isolated DNA sequences, and isolated RNA sequences. Polynucleotides that can be used in the methods of this disclosure may comprise natural nucleic acid sequences and their variants, artificial nucleic acid sequences, or combinations of such sequences.

[0103] The term "oligonucleotide" refers to a relatively short nucleic acid, such as a nucleic acid less than 100 nucleotides in length. Oligonucleotides can be single-stranded or double-stranded. Oligonucleotides can include naturally occurring ribonucleotides, naturally occurring deoxyribonucleotides, and / or nucleotides with one or more modifications to naturally occurring ends, sugars, nucleotide bases, and / or internucleotide bonds. Non-limiting examples of oligonucleotides include double-stranded oligonucleotides, single-stranded oligonucleotides, antisense oligonucleotides, small interfering RNA (siRNA), microRNA mimics, short hairpin RNA (shRNA), single-stranded small interfering RNA (ssRNAi), RNaseH oligonucleotides, anti-microRNA oligonucleotides, steric cleavage oligonucleotides, exon-jumping oligonucleotides, CRISPR guide RNAs, and aptamers.

[0104] The term "double-stranded oligonucleotide" refers to an oligonucleotide that is essentially in the form of a double strand. Double-stranded oligonucleotides can include structures in which the double-stranded region is formed between two non-covalently linked antiparallel oligonucleotides, as in siRNA or microRNA mimics. Such double-stranded oligonucleotides may have short nucleotide overhangs at one or both ends of the double-stranded structure. Double-stranded oligonucleotides can also contain a single oligonucleotide of sufficient length and self-complementarity to form a double-stranded structure, as in shRNA. Such double-stranded oligonucleotides contain stem-loop structures. Double-stranded nucleic acids may contain one or more modifications relating to naturally occurring ends, sugars, nucleotide bases, and / or phosphate groups. Non-limiting examples of double-stranded oligonucleotides include small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA mimics.

[0105] The term "small interfering RNA" or "siRNA" refers to a double-stranded oligonucleotide consisting of separate antisense and sense strands. It interferes with gene expression in a sequence-specific manner by promoting pre-translational mRNA degradation through the RNA interference pathway. The antisense and sense strands of siRNA are not covalently linked.

[0106] The term "microRNA mimic" refers to a synthetic version of a naturally occurring microRNA. A microRNA mimic includes an antisense strand complementary to one or more target mRNAs and a sense strand complementary to the antisense strand. In naturally occurring microRNAs, the antisense strand is typically only partially complementary to its target mRNA, and the sense strand is only partially complementary to the antisense strand. A microRNA mimic can include a nucleobase sequence that is 100% identical to a naturally occurring microRNA, or it can include a nucleobase sequence that is less than 100% identical to a naturally occurring microRNA. For example, a microRNA mimic can include a sense strand that is 100% complementary to the antisense strand.

[0107] The term "single-stranded RNA interference" or "ssRNAi" refers to single-stranded oligonucleotides that interfere with gene expression in a sequence-specific manner by promoting the degradation of pre-translational mRNA through the RNA interference pathway.

[0108] The term "antisense strand" refers to an oligonucleotide of siRNA or ssRNAi that is complementary to the target mRNA and incorporated into the RNA-induced silencing complex (RISC) to guide gene silencing in a sequence-specific manner via the RNA interference pathway. Antisense strands can also be called "guide strands."

[0109] The term "sense chain" refers to an oligonucleotide that is complementary to the antisense chain of a double-stranded oligonucleotide. The sense chain typically degrades after the antisense chain is incorporated into RISC. The sense chain can also be called a "lagging chain."

[0110] The term "double-stranded region" refers to a structure formed by nucleotide base pairing of complementary oligonucleotide sequences. A double-stranded region can be formed from a portion of the complementary sequence or from the full length of the complementary sequence.

[0111] The term "short hairpin RNA" or "shRNA" refers to a double-stranded oligonucleotide contained in a loop structure that is processed into siRNA in the cell. This double-stranded oligonucleotide promotes the degradation of pre-translational mRNA through the RNA interference pathway, thereby interfering with gene expression in a sequence-specific manner.

[0112] The term "nucleotide overhang" refers to the continuous single-stranded nucleotides at the end of the oligonucleotide in a double-stranded oligonucleotide.

[0113] The term "single-stranded oligonucleotide" refers to an oligonucleotide that does not hybridize with its complementary strand. Non-restrictive examples of single-stranded oligonucleotides include single-stranded small interfering RNA (ssRNAi), RNaseH oligonucleotides (oligonucleotides chemically modified to induce RNaseH-mediated degradation of target RNA), anti-microRNA oligonucleotides (oligonucleotides complementary to microRNA), steric-blocking oligonucleotides (oligonucleotides that interfere with target RNA activity without degrading the target RNA), exon-jugating oligonucleotides (oligonucleotides that hybridize with exon adhesion sites and alter splicing), CRISPR guide RNAs, and aptamers.

[0114] The term "hybridization" refers to the binding of one nucleic acid to another based on the complementarity of their nucleobase sequences. In this example, the antisense strand hybridizes with the sense strand. In this example, the antisense strand hybridizes with the target mRNA sequence.

[0115] The term "complementary" refers to nucleobases that have the ability to pair non-covalently via hydrogen bonding.

[0116] The term "completely complementary" means that each nucleobase of the first nucleic acid is complementary to each nucleobase of the second nucleic acid. In the embodiments, the antisense strand is completely complementary to its target mRNA. In the embodiments, the sense and antisense strands of the double-stranded oligonucleotide are completely complementary along their entire length. In the embodiments, the sense and antisense strands of the double-stranded oligonucleotide are completely complementary along the entire length of the double-stranded region of the siRNA, and one or both ends of either strand include a single-stranded nucleotide.

[0117] The term "nucleoside" refers to a monomer of a nucleotide base and a pentafuranosyl sugar (e.g., ribose or deoxyribose). Nucleosides can be modified at the nucleotide base and / or sugar. In the examples, the nucleoside is a deoxyribonucleoside. In the examples, the nucleoside is a ribonucleoside.

[0118] The term "nucleotide" refers to a nucleoside covalently linked to a phosphate ester group at the 5' carbon of a pentafuranosyl sugar. Nucleotides can be modified at one or more of the nucleobase, sugar, or phosphate ester groups. Nucleotides can be linked to ligands directly or via linkers. In the examples, the nucleotide is a deoxyribonucleotide. In the examples, the nucleotide is a ribonucleotide.

[0119] The term "nucleobase" refers to the heterocyclic base portion of a nucleoside or nucleotide. Non-limiting examples of nucleobases include cytosine or derivatives thereof (e.g., cytosine analogs), guanine or derivatives thereof (e.g., guanine analogs), adenine or derivatives thereof (e.g., adenine analogs), thymine or derivatives thereof (e.g., thymine analogs), uracil or derivatives thereof (e.g., uracil analogs), hypoxanthine or derivatives thereof (e.g., hypoxanthine analogs), xanthine or derivatives thereof (e.g., xanthine analogs), 7-methylguanine or derivatives thereof (…). For example, 7-methylguanine analogues), denitro-adenine or derivatives thereof (e.g., denitro-adenine analogues), denitro-guanine or derivatives thereof (e.g., denitroguanine), denitro-hypoxanthine or derivatives thereof, 5,6-dihydrouracil or derivatives thereof (e.g., 5,6-dihydrouracil analogues), 5-methylcytosine or derivatives thereof (e.g., 5-methylcytosine analogues), or 5-hydroxymethylcytosine or derivatives thereof (e.g., 5-hydroxymethylcytosine analogues). In embodiments, the nucleobase is optionally adenine, guanine, hypoxanthine, xanthine, theobromine, caffeine, uric acid, or isoguanine. In embodiments, the nucleobase is... , , or The nucleobases may optionally be substituted or modified.

[0120] The term "modified nucleotide" refers to a nucleotide that has one or more modifications relative to a naturally occurring nucleotide. Modifications can be present in the nucleotide's nucleoside internucleotides, nucleobases, and / or sugar moieties. Modified nucleotides are chosen over unmodified forms due to desired properties, such as enhanced cellular uptake, enhanced affinity for other oligonucleotides or nucleic acid targets, increased stability in the presence of nucleases, and / or reduced immune stimulation. Modified nucleotides may have a modified sugar moieties and unmodified phosphate groups. Nucleic acids, polynucleotides, and oligonucleotides may include one or more modified nucleotides.

[0121] As used herein, the term "complement" refers to a nucleotide (e.g., RNA or DNA) or nucleotide sequence capable of base pairing with a complementary nucleotide or nucleotide sequence. As described herein and known in the art, the complementary (matching) nucleotide of adenosine is thymidine, and the complementary (matching) nucleotide of guanine is cytosine. Therefore, a complement can comprise a nucleotide sequence that bases to the corresponding complementary nucleotide of a second nucleic acid sequence. The nucleotides of the complement can partially or completely match the nucleotides of the second nucleic acid sequence. When the nucleotides of the complement completely match each nucleotide in the second nucleic acid sequence, the complement forms a base pair with each nucleotide in the second nucleic acid sequence. When the nucleotides of the complement partially match the nucleotides of the second nucleic acid sequence, only some nucleotides in the complement form a base pair with the nucleotides of the second nucleic acid sequence. Examples of complementary sequences include coding and non-coding sequences, where the non-coding sequence contains a complementary nucleotide of the coding sequence, and thus forms a complement of the coding sequence. Further examples of complementary sequences are sense sequences and antisense sequences, where the sense sequence contains a complementary nucleotide of the antisense sequence, and thus forms a complement of the antisense sequence.

[0122] As described herein, sequence complementarity can be partial, where only some of the nucleic acids match according to base pairing, or complete, where all nucleic acids match according to base pairing. Thus, two sequences complementary to each other can have a specified percentage of nucleotides involved in nucleobase pairing (i.e., approximately 60% complementarity within a specified region, preferably 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or higher complementarity).

[0123] “Hybridization” should be understood as the attachment of one single-stranded nucleic acid (such as a primer) to another nucleic acid based on the well-known principle of sequence complementarity. In this example, the other nucleic acid is a single-stranded nucleic acid. The tendency for nucleic acids to hybridize depends on the temperature and ionic strength of their environment, the length of the nucleic acids, and the degree of complementarity. The effects of these parameters on hybridization are described, for example, in Sambrook J, Fritsch EF., Maniatis T., *Molecular Cloning: A Laboratory Manual*, Cold Spring Harbor Laboratory Press, New York (1989). As used herein, hybridization of primers or DNA extension products can be achieved by forming phosphodiester bonds with available nucleotides or nucleotide analogs capable of forming phosphodiester bonds.

[0124] In the context of two or more nucleic acid or polypeptide sequences, the term "identical" or "percentage of identity" means that two or more sequences or subsequences are identical or have a specified percentage of identical amino acid residues or nucleotides (i.e., at least 60% identity within a specified region when comparing and aligning maximum correspondence within a comparison window or specified region, or at least 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or within the range defined by any two of the foregoing values), as if using the BLAST or BLAST 2.0 sequence comparison algorithm with the default parameters described below or measured by manual alignment and visual inspection (see, for example, the NCBI website, etc.). This definition also relates to, or can be applied to, complements of the test sequence. The definition also includes sequences with deletions and / or additions, as well as sequences with substitutions. As described below, preferred algorithms can address gaps, insertions, and other issues. Alignment used to determine the percentage of sequence identity can be implemented in various ways within the scope of the art, such as using publicly available computer software like BLAST, BLAST-2, ALIGN, ALIGN-2, or Megalign (DNASTAR) software. Appropriate parameters used to measure alignment (including any algorithm required to achieve maximum alignment across the full length of the sequences being compared) can be determined by known methods.

[0125] compound

[0126] In particular, compounds are provided comprising nucleic acids (A) covalently bonded to one or more half-life extension motifs (HLEMs). For example, said compounds comprise nucleic acids (A) covalently bonded to one, two, three, four, or five half-life extension motifs (HLEMs).

[0127] On the one hand, the compound has formula (I): (HLEM) z -A (I), Where z is an integer from 1 to 5.

[0128] In this embodiment, z is 1. In this embodiment, z is 2. In this embodiment, z is 3. In this embodiment, z is 4. In this embodiment, z is 5.

[0129] On the one hand, the nucleic acid is covalently bonded to one or more uptake motifs (UM). For example, the nucleic acid is covalently bonded to one, two, three, four, or five uptake motifs (UM).

[0130] On the one hand, the compound has formula (II): (HLEM) z -A-(UM) t (II) Where t is an integer from 1 to 5.

[0131] In this embodiment, t is 1. In this embodiment, t is 2. In this embodiment, t is 3. In this embodiment, t is 4. In this embodiment, t is 5.

[0132] In an embodiment, the half-life-extending motif has the following structure: (III). k is an integer from 1 to 5.

[0133] L 1 Independently covalent linkers. L 2 It is an unsubstituted alkylene group on its own.

[0134] In this embodiment, k is 1. In this embodiment, k is 2. In this embodiment, k is 3. In this embodiment, k is 4. In this embodiment, k is 5. In this embodiment, k is an integer from 1 to 3. In this embodiment, k is an integer from 1 to 2.

[0135] In an embodiment, one or more L 2 Can be with L 1One or more atomic connections in. In an embodiment, one or more L 2 Can be with L 1 One or more atoms in the L are connected, and the one or more atoms may be the same or different. In an embodiment, one or more L 2 They can be connected to the same atoms. In the embodiment, one or more L... 2 It can be connected to different atoms. In the embodiment, one or more L... 2 It can be connected to the same or different atoms.

[0136] In an embodiment, one or more L 2 Can be used independently with L 1A L 1B L 1C L 1D or L 1E Connection. In this embodiment, L 2 Can be used independently with L 1A Connection. In an embodiment, an L 2 Can be used independently with L 1B Connection. In an embodiment, an L 2 Can be used independently with L 1C Connection. In an embodiment, an L 2 Can be used independently with L 1D Connection. In an embodiment, an L 2 Can be used independently with L 1E connect.

[0137] In the embodiment, L 1A L 1B L 1C L 1D and L 1E Independently for the bond, -N(R) 20 )-, -O-, -S-, -C(O)-, -N(R 20 )C(O)-、-C(O)N(R 21 )-、-N(R 20 )C(O)N(R 21 -, -C(O)O-, -OC(O)-, -N(R) 20 )C(O)O-、-OC(O)N(R 21 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(S)(R 22 )-O-、-OP(O)(NR 20 R 21 -N-、-OP(S)(NR) 20 R21 )-N-、-OP(O)(NR 20 R 21 )-O-、-OP(S)(NR 20 R 21 )-O-、-P(O)(NR 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 )-O-、-P(S)(NR 20 R 21 -O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. Each R 20 R 21 and R 22 Independently hydrogen or unsubstituted C1-C 10 alkyl.

[0138] In an embodiment, one or more L 2 Can be used independently with L 1A L 1B L 1C L 1D or L 1E Connection. In an embodiment, one or more L 2 Can be used independently with L 1A Connection. In an embodiment, one or more L 2 Can be used independently with L 1B Connection. In an embodiment, one or more L 2 Can be used independently with L 1C Connection. In an embodiment, one or more L 2 Can be used independently with L 1D Connection. In an embodiment, one or more L 2 Can be used independently with L 1E connect.

[0139] In an embodiment, at least one L 2 Can be used independently with L 1A Connection. In an embodiment, at least one L 2 Can be used independently with L 1B Connection. In an embodiment, at least one L 2 Can be used independently with L 1C Connection. In an embodiment, at least one L 2Can be used independently with L 1D Connection. In an embodiment, at least one L 2 Can be used independently with L 1E connect.

[0140] In the embodiment, an L 2 Can be used independently with L 1A Connection. In an embodiment, an L 2 Can be used independently with L 1B Connection. In an embodiment, an L 2 Can be used independently with L 1C Connection. In an embodiment, an L 2 Can be used independently with L 1D Connection. In an embodiment, an L 2 Can be used independently with L 1E connect.

[0141] In the embodiment, L 1A For key, -N(R) 20 )-, -O-, -S-, -C(O)-, -N(R 20 )C(O)-、-C(O)N(R 21 )-、-N(R 20 )C(O)N(R 21 -, -C(O)O-, -OC(O)-, -N(R) 20 )C(O)O-、-OC(O)N(R 21 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(S)(R 22 )-O-、-OP(O)(NR 20 R 21 -N-、-OP(S)(NR) 20 R 21 )-N-、-OP(O)(NR 20 R 21 )-O-、-OP(S)(NR 20 R 21 )-O-、-P(O)(NR 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 )-O-、-P(S)(NR 20 R 21-O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene.

[0142] In the embodiment, L 1A As a key. In the embodiment, L 1A -N(R) 20 In the embodiment, L 1A It is either -O- or -S-. In the embodiment, L 1A It is -C(O)-. In the embodiment, L 1A -N(R) 20 C(O)- or -C(O)N(R) 21 In the embodiment, L 1A -N(R) 20 )C(O)N(R 21 In the embodiment, L 1A It is -C(O)O- or -OC(O)-. In the embodiment, L 1A -N(R) 20 )C(O)O-or-OC(O)N(R 21 In the embodiment, L 1A is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(O)(NR 20 R 21 )-N- or OP(O)(NR 20 R 21 )-O-. In the embodiment, L 1A -P(O)(NR) 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 -O- or -P(S)(NR) 20 R 21 )-O-. In the embodiment, L 1A It is -SS-.

[0143] In the embodiment, L 1A Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1AIndependently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1A Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1A Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 1A Independently for substituted C1-C 20 Alkylene. In the examples, L 1A Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 1A Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 1A Independently for substituted C1-C 12 Alkylene. In the examples, L 1A Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 1A Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1A Independently, it is a substituted C1-C8 alkylene group. In the examples, L 1A Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 1A Independently, it is a substituted C1-C6 alkylene group. In the examples, L 1A Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 1A Independently, it is a substituted C1-C4 alkylene group. In the examples, L 1A Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 1A Independently, it is either substituted or unsubstituted ethylene. In the examples, L 1A Independently, it is a substituted ethylene. In the examples, L 1A Independently, it is an unsubstituted ethylene. In the examples, L 1A Independently, it is a substituted or unsubstituted methylene group. In the examples, L 1AIndependently, it is a substituted methylene group. In the examples, L 1A Independently, it is an unsubstituted methylene group.

[0144] In the embodiment, L 1A Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 20 ternary, 2 to 12 ternary, 2 to 8 ternary, 2 to 6 ternary, 4 to 6 ternary, 2 to 3 ternary, or 4 to 5 ternary). In the examples, L 1A Independently, it is a substituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1A Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted 2- to 20-membered heteroalkylene group. In the examples, L 1A Independently, it is an unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1A Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 1A Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted 4- to 6-membered heteroalkylene group. In the examples, L 1A Independently, it is an unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- or 3-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted 2- to 3-membered heteroalkylene group. In the examples, L 1A Independently, it is an unsubstituted 2- to 3-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 4- to 5-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted 4- to 5-membered heteroalkylene group. In the examples, L 1AIndependently, it is an unsubstituted 4- to 5-membered heteroalkylene group.

[0145] In the embodiment, L 1B For key, -N(R) 20 )-, -O-, -S-, -C(O)-, -N(R 20 )C(O)-、-C(O)N(R 21 )-、-N(R 20 )C(O)N(R 21 -, -C(O)O-, -OC(O)-, -N(R) 20 )C(O)O-、-OC(O)N(R 21 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(S)(R 22 )-O-、-OP(O)(NR 20 R 21 -N-、-OP(S)(NR) 20 R 21 )-N-、-OP(O)(NR 20 R 21 )-O-、-OP(S)(NR 20 R 21 )-O-、-P(O)(NR 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 )-O-、-P(S)(NR 20 R 21 -O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene.

[0146] In the embodiment, L 1B As a key. In the embodiment, L 1B -N(R) 20 In the embodiment, L 1B It is either -O- or -S-. In the embodiment, L 1B It is -C(O)-. In the embodiment, L 1B -N(R) 20 C(O)- or -C(O)N(R) 21 In the embodiment, L 1B -N(R)20 )C(O)N(R 21 In the embodiment, L 1B It is -C(O)O- or -OC(O)-. In the embodiment, L 1B -N(R) 20 )C(O)O-or-OC(O)N(R 21 In the embodiment, L 1B is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(O)(NR 20 R 21 )-N- or OP(O)(NR 20 R 21 )-O-. In the embodiment, L 1B -P(O)(NR) 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 -O- or -P(S)(NR) 20 R 21 )-O-. In the embodiment, L 1B It is -SS-.

[0147] In the embodiment, L 1B Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1B Independently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1B Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1B Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 1B Independently for substituted C1-C 20 Alkylene. In the examples, L 1B Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 1BIndependently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 1B Independently for substituted C1-C 12 Alkylene. In the examples, L 1B Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 1B Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1B Independently, it is a substituted C1-C8 alkylene group. In the examples, L 1B Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 1B Independently, it is a substituted C1-C6 alkylene group. In the examples, L 1B Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 1B Independently, it is a substituted C1-C4 alkylene group. In the examples, L 1B Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 1B Independently, it is either substituted or unsubstituted ethylene. In the examples, L 1B Independently, it is a substituted ethylene. In the examples, L 1B Independently, it is an unsubstituted ethylene. In the examples, L 1B Independently, it is a substituted or unsubstituted methylene group. In the examples, L 1B Independently, it is a substituted methylene group. In the examples, L 1B Independently, it is an unsubstituted methylene group.

[0148] In the embodiment, L 1B Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 20 ternary, 2 to 12 ternary, 2 to 8 ternary, 2 to 6 ternary, 4 to 6 ternary, 2 to 3 ternary, or 4 to 5 ternary). In the examples, L 1B Independently, it is a substituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1B Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L1B Independently, it is a substituted 2- to 20-membered heteroalkylene group. In the examples, L 1B Independently, it is an unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1B Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 1B Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted 4- to 6-membered heteroalkylene group. In the examples, L 1B Independently, it is an unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- or 3-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted 2- to 3-membered heteroalkylene group. In the examples, L 1B Independently, it is an unsubstituted 2- to 3-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 4- to 5-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted 4- to 5-membered heteroalkylene group. In the examples, L 1B Independently, it is an unsubstituted 4- to 5-membered heteroalkylene group.

[0149] In the embodiment, L 1C For key, -N(R) 20 )-, -O-, -S-, -C(O)-, -N(R 20 )C(O)-、-C(O)N(R 21 )-、-N(R 20 )C(O)N(R 21 -, -C(O)O-, -OC(O)-, -N(R) 20 )C(O)O-、-OC(O)N(R 21 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(S)(R 22 )-O-、-OP(O)(NR 20 R21 -N-、-OP(S)(NR) 20 R 21 )-N-、-OP(O)(NR 20 R 21 )-O-、-OP(S)(NR 20 R 21 )-O-、-P(O)(NR 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 )-O-、-P(S)(NR 20 R 21 -O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene.

[0150] In the embodiment, L 1C As a key. In the embodiment, L 1C -N(R) 20 In the embodiment, L 1C It is either -O- or -S-. In the embodiment, L 1C It is -C(O)-. In the embodiment, L 1C -N(R) 20 C(O)- or -C(O)N(R) 21 In the embodiment, L 1C -N(R) 20 )C(O)N(R 21 In the embodiment, L 1C It is -C(O)O- or -OC(O)-. In the embodiment, L 1C -N(R) 20 )C(O)O-or-OC(O)N(R 21 In the embodiment, L 1C is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(O)(NR 20 R 21 )-N- or OP(O)(NR 20 R 21 )-O-. In the embodiment, L 1C -P(O)(NR) 20 R 21-N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 -O- or -P(S)(NR) 20 R 21 )-O-. In the embodiment, L 1C It is -SS-.

[0151] In the embodiment, L 1C Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1C Independently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1C Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1C Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 1C Independently for substituted C1-C 20 Alkylene. In the examples, L 1C Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 1C Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 1C Independently for substituted C1-C 12 Alkylene. In the examples, L 1C Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 1C Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1C Independently, it is a substituted C1-C8 alkylene group. In the examples, L 1C Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 1C Independently, it is a substituted C1-C6 alkylene group. In the examples, L 1CIndependently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 1C Independently, it is a substituted C1-C4 alkylene group. In the examples, L 1C Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 1C Independently, it is either substituted or unsubstituted ethylene. In the examples, L 1C Independently, it is a substituted ethylene. In the examples, L 1C Independently, it is an unsubstituted ethylene. In the examples, L 1C Independently, it is a substituted or unsubstituted methylene group. In the examples, L 1C Independently, it is a substituted methylene group. In the examples, L 1C Independently, it is an unsubstituted methylene group.

[0152] In the embodiment, L 1C Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 20 ternary, 2 to 12 ternary, 2 to 8 ternary, 2 to 6 ternary, 4 to 6 ternary, 2 to 3 ternary, or 4 to 5 ternary). In the examples, L 1C Independently, it is a substituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1C Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1C Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 2- to 20-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1CIndependently, it is a substituted or unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 4- to 6-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted 2- or 3-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 2- to 3-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 2- to 3-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted 4- to 5-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 4- to 5-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 4- to 5-membered heteroalkylene group.

[0153] In the embodiment, L 1D For key, -N(R) 20 )-, -O-, -S-, -C(O)-, -N(R 20 )C(O)-、-C(O)N(R 21 )-、-N(R 20 )C(O)N(R 21 -, -C(O)O-, -OC(O)-, -N(R) 20 )C(O)O-、-OC(O)N(R 21 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(S)(R 22 )-O-、-OP(O)(NR 20 R 21 -N-、-OP(S)(NR) 20 R 21 )-N-、-OP(O)(NR 20 R 21 )-O-、-OP(S)(NR 20 R 21 )-O-、-P(O)(NR 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 )-O-、-P(S)(NR 20 R 21-O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene.

[0154] In the embodiment, L 1D As a key. In the embodiment, L 1D -N(R) 20 In the embodiment, L 1D It is either -O- or -S-. In the embodiment, L 1D It is -C(O)-. In the embodiment, L 1D -N(R) 20 C(O)- or -C(O)N(R) 21 In the embodiment, L 1D -N(R) 20 )C(O)N(R 21 In the embodiment, L 1D It is -C(O)O- or -OC(O)-. In the embodiment, L 1D -N(R) 20 )C(O)O-or-OC(O)N(R 21 In the embodiment, L 1D is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(O)(NR 20 R 21 )-N- or OP(O)(NR 20 R 21 )-O-. In the embodiment, L 1D -P(O)(NR) 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 -O- or -P(S)(NR) 20 R 21 )-O-. In the embodiment, L 1D It is -SS-.

[0155] In the embodiment, L 1D Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1DIndependently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1D Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1D Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 1D Independently for substituted C1-C 20 Alkylene. In the examples, L 1D Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 1D Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 1D Independently for substituted C1-C 12 Alkylene. In the examples, L 1D Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 1D Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1D Independently, it is a substituted C1-C8 alkylene group. In the examples, L 1D Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 1D Independently, it is a substituted C1-C6 alkylene group. In the examples, L 1D Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 1D Independently, it is a substituted C1-C4 alkylene group. In the examples, L 1D Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 1D Independently, it is either substituted or unsubstituted ethylene. In the examples, L 1D Independently, it is a substituted ethylene. In the examples, L 1D Independently, it is an unsubstituted ethylene. In the examples, L 1D Independently, it is a substituted or unsubstituted methylene group. In the examples, L 1DIndependently, it is a substituted methylene group. In the examples, L 1D Independently, it is an unsubstituted methylene group.

[0156] In the embodiment, L 1D Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 20 ternary, 2 to 12 ternary, 2 to 8 ternary, 2 to 6 ternary, 4 to 6 ternary, 2 to 3 ternary, or 4 to 5 ternary). In the examples, L 1D Independently, it is a substituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1D Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1D Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 2- to 20-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 4- to 6-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 2- or 3-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 2- to 3-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 2- to 3-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 4- to 5-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 4- to 5-membered heteroalkylene group. In the examples, L 1DIndependently, it is an unsubstituted 4- to 5-membered heteroalkylene group.

[0157] In the embodiment, L 1E For key, -N(R) 20 )-, -O-, -S-, -C(O)-, -N(R 20 )C(O)-、-C(O)N(R 21 )-、-N(R 20 )C(O)N(R 21 -, -C(O)O-, -OC(O)-, -N(R) 20 )C(O)O-、-OC(O)N(R 21 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(S)(R 22 )-O-、-OP(O)(NR 20 R 21 -N-、-OP(S)(NR) 20 R 21 )-N-、-OP(O)(NR 20 R 21 )-O-、-OP(S)(NR 20 R 21 )-O-、-P(O)(NR 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 )-O-、-P(S)(NR 20 R 21 -O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene.

[0158] In the embodiment, L 1E As a key. In the embodiment, L 1E -N(R) 20 In the embodiment, L 1E It is either -O- or -S-. In the embodiment, L 1E It is -C(O)-. In the embodiment, L 1E -N(R) 20 C(O)- or -C(O)N(R) 21 In the embodiment, L 1E -N(R)20 )C(O)N(R 21 In the embodiment, L 1E It is -C(O)O- or -OC(O)-. In the embodiment, L 1E -N(R) 20 )C(O)O-or-OC(O)N(R 21 In the embodiment, L 1E is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 22 )-O-、-OP(O)(NR 20 R 21 )-N- or OP(O)(NR 20 R 21 )-O-. In the embodiment, L 1E -P(O)(NR) 20 R 21 -N-、-P(S)(NR) 20 R 21 -N-、-P(O)(NR) 20 R 21 -O- or -P(S)(NR) 20 R 21 )-O-. In the embodiment, L 1E It is -SS-.

[0159] In the embodiment, L 1E Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1E Independently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1E Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 1E Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 1E Independently for substituted C1-C 20 Alkylene. In the examples, L 1E Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 1EIndependently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 1E Independently for substituted C1-C 12 Alkylene. In the examples, L 1E Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 1E Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1E Independently, it is a substituted C1-C8 alkylene group. In the examples, L 1E Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 1E Independently, it is a substituted C1-C6 alkylene group. In the examples, L 1E Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 1E Independently, it is a substituted C1-C4 alkylene group. In the examples, L 1E Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 1E Independently, it is either substituted or unsubstituted ethylene. In the examples, L 1E Independently, it is a substituted ethylene. In the examples, L 1E Independently, it is an unsubstituted ethylene. In the examples, L 1E Independently, it is a substituted or unsubstituted methylene group. In the examples, L 1E Independently, it is a substituted methylene group. In the examples, L 1E Independently, it is an unsubstituted methylene group.

[0160] In the embodiment, L 1E Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 20 ternary, 2 to 12 ternary, 2 to 8 ternary, 2 to 6 ternary, 4 to 6 ternary, 2 to 3 ternary, or 4 to 5 ternary). In the examples, L 1E Independently, it is a substituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1E Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 1E Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L1E Independently, it is a substituted 2- to 20-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 4- to 6-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 2- or 3-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 2- to 3-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 2- to 3-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 4- to 5-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 4- to 5-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 4- to 5-membered heteroalkylene group.

[0161] In the embodiment, each R 20 R 21 and R 22 Independently hydrogen or unsubstituted C1-C 10 alkyl.

[0162] In the embodiment, R 20 Independently hydrogen or unsubstituted C1-C 10 Alkyl group. In the examples, R 20 Independently hydrogen. In the examples, R 20 For unreplaced C1-C 10 Alkyl group. In the examples, R 20 It is an unsubstituted C1-C8 alkyl group. In the examples, R 20 It is an unsubstituted C1-C6 alkyl group. In the examples, R20 It is an unsubstituted C1-C5 alkyl group. In the examples, R 20 It is an unsubstituted C1-C4 alkyl group. In the examples, R 20 It is an unsubstituted C1-C3 alkyl group. In the examples, R 20 R is an unsubstituted methyl group. In the examples, R 20 It is an unsubstituted ethyl group. In the examples, R... 20 It is an unsubstituted propyl group. In the examples, R 20 It is an unsubstituted isopropyl group. In the examples, R 20 It is an unsubstituted n-butyl. In the examples, R 20 It is unsubstituted tert-butyl. In the embodiment, R 20 It is an unsubstituted 2-butyl. In the examples, R 20 It is an unsubstituted isobutyl group.

[0163] In the embodiment, R 21 Independently hydrogen or unsubstituted C1-C 10 Alkyl group. In the examples, R 21 Independently hydrogen. In the examples, R 21 For unreplaced C1-C 10 Alkyl group. In the examples, R 21 It is an unsubstituted C1-C8 alkyl group. In the examples, R 21 It is an unsubstituted C1-C6 alkyl group. In the examples, R 21 It is an unsubstituted C1-C5 alkyl group. In the examples, R 21 It is an unsubstituted C1-C4 alkyl group. In the examples, R 21 It is an unsubstituted C1-C3 alkyl group. In the examples, R 21 R is an unsubstituted methyl group. In the examples, R 21 It is an unsubstituted ethyl group. In the examples, R... 21 It is an unsubstituted propyl group. In the examples, R 21 It is an unsubstituted isopropyl group. In the examples, R 21 It is an unsubstituted n-butyl. In the examples, R 21 It is unsubstituted tert-butyl. In the embodiment, R 21 It is an unsubstituted 2-butyl. In the examples, R 21 It is an unsubstituted isobutyl group.

[0164] In the embodiment, R 22 Independently hydrogen or unsubstituted C1-C 10 Alkyl group. In the examples, R 22 Independently hydrogen. In the examples, R22 For unreplaced C1-C 10 Alkyl group. In the examples, R 22 It is an unsubstituted C1-C8 alkyl group. In the examples, R 22 It is an unsubstituted C1-C6 alkyl group. In the examples, R 22 It is an unsubstituted C1-C5 alkyl group. In the examples, R 22 It is an unsubstituted C1-C4 alkyl group. In the examples, R 22 It is an unsubstituted C1-C3 alkyl group. In the examples, R 22 R is an unsubstituted methyl group. In the examples, R 22 It is an unsubstituted ethyl group. In the examples, R... 22 It is an unsubstituted propyl group. In the examples, R 22 It is an unsubstituted isopropyl group. In the examples, R 22 R22 is unsubstituted n-butyl. In an embodiment, R22 is unsubstituted tert-butyl. In an embodiment, R22 is unsubstituted 2-butyl. In an embodiment, R22 is unsubstituted isobutyl.

[0165] In the embodiment, R 20 R 21 and R 22 Each of these is independently hydrogen or an unsubstituted C1-C3 alkyl group. In the examples, R 20 For hydrogen, and each R 21 and R 22 Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 21 For hydrogen, and each R 20 and R 22 Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 22 For hydrogen, and each R 20 and R 21 Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 20 R 21 and R 22 It is hydrogen. In the examples, R is... 20 It is an unsubstituted C1-C3 alkyl group, and R 21 and R 22 Hydrogen. In the examples, R 21 It is an unsubstituted C1-C3 alkyl group, and R 20 and R 22 Hydrogen. In the examples, R 22 It is an unsubstituted C1-C3 alkyl group, and R 20 and R 21 Hydrogen. In the examples, R20 R 21 and R 22 Each of them is independently an unsubstituted C1-C3 alkyl group.

[0166] In the embodiment, L 2 Independent for unsubstituted C2-C 24 Alkylene. In the examples, L 2 Independent for unsubstituted C2-C 22 Alkylene. In the examples, L 2 Independent for unreplaced C5-C 22 Alkylene. In the examples, L 2 Independently for unreplaced C 10 -C 22 Alkylene. In the examples, L 2 Independently for unreplaced C 12 -C 22 Alkylene. In the examples, L 2 Independently for unreplaced C 10 -C 20 Alkylene. In the examples, L 2 Independently for unreplaced C 12 -C 20 Alkylene. In the examples, L 2 Independently for unreplaced C 10 -C 18 Alkylene. In the examples, L 2 Independently for unreplaced C 12 -C 18 Alkylene. In the examples, L 2 Independently for unreplaced C 10 -C 16 Alkylene. In the examples, L 2 Independently for unreplaced C 12 -C 16 Alkylene. In the examples, L 2 Independently for unreplaced C 14 -C 16 Alkylene. In the examples, L 2 Independently for unreplaced C 14 -C 15 Alkylene. In the examples, L 2 Independently for unreplaced C 14 Alkylene. In the examples, L 2 Independently for unreplaced C 15 Alkylene. In the examples, L 2 Independently for unreplaced C 16 Alkylene.

[0167] In the embodiment, L 2 Independently unsubstituted, unbranched C2-C 24 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C2-C 22 Alkylene. In the examples, L 2 Independent for unsubstituted, unbranched C5-C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 10 -C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 12 -C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 10 -C 20 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 12 -C 20 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 10 -C 18 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 12 -C 18 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 10 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 12 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 14 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 14 -C 15 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 14 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 15 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched C 16 Alkylene.

[0168] In the embodiment, L 2 Independently for unsubstituted, unbranched saturated C2-C 24 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C2-C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C5-C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 10 -C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 12 -C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 10 -C 20 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 12 -C 20 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 10 -C 18 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 12 -C 18 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 10 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 12 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 14 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 14 -C 15 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 14 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 15 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched saturated C 16Alkylene.

[0169] In the embodiment, L 2 Independently unsubstituted, unbranched, unsaturated C2-C 24 Alkylene. In the examples, L 2 Independently unsubstituted, unbranched, unsaturated C2-C 22 Alkylene. In the examples, L 2 Independently unsubstituted, unbranched, unsaturated C5-C 22 Alkylene. In the examples, L 2 Independently unsubstituted, unbranched, unsaturated C 10 -C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched, unsaturated C 12 -C 22 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched, unsaturated C 10 -C 20 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched, unsaturated C 12 -C 20 Alkylene. In the examples, L 2 Independently unsubstituted, unbranched, unsaturated C 10 -C 18 Alkylene. In the examples, L 2 Independently unsubstituted, unbranched, unsaturated C 12 -C 18 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched, unsaturated C 10 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched, unsaturated C 12 -C 16 Alkylene. In the examples, L 2 Independently unsubstituted, unbranched, unsaturated C 14 -C 16 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched, unsaturated C 14 -C 15 Alkylene. In the examples, L 2 Independently unsubstituted, unbranched, unsaturated C 14 Alkylene. In the examples, L 2 Independently for unsubstituted, unbranched, unsaturated C 15 Alkylene. In the examples, L2 Independently for unsubstituted, unbranched, unsaturated C 16 Alkylene.

[0170] In the embodiment, L 1 The maximum size is less than 200 angstroms. In the embodiment, L 1 The maximum size is less than 190 angstroms. In the embodiment, L 1 The maximum size is less than 180 angstroms. In the embodiment, L 1 The maximum size is less than 170 angstroms. In the embodiment, L 1 The maximum size is less than 160 angstroms. In the embodiment, L 1 The maximum size is less than 150 angstroms. In the embodiment, L 1 The maximum size is less than 140 angstroms. In the embodiment, L 1 The maximum size is less than 130 angstroms. In the embodiment, L 1 The maximum size is less than 120 angstroms. In the embodiment, L 1 The maximum size is less than 110 angstroms. In the embodiment, L 1 The maximum size is less than 100 angstroms. In the embodiment, L 1 The maximum size is less than 90 angstroms. In the embodiment, L 1 The maximum size is less than 80 angstroms. In the embodiment, L 1 The maximum size is less than 70 angstroms. In the embodiment, L 1 The maximum size is less than 60 angstroms. In the embodiment, L 1 The maximum size is less than 50 angstroms. In the embodiment, L 1 The maximum size is less than 40 angstroms. In the embodiment, L 1 The maximum size is less than 30 angstroms. In the embodiment, L 1 The maximum size is less than 20 angstroms. In the embodiment, L 1 The maximum size is less than 10 angstroms.

[0171] In the embodiment, L 1A L 1B L 1C L 1D and L 1E Each of them has a maximum size that is independently less than 50 angstroms. In the embodiment, L 1A L 1B L 1C L 1D and L 1E Each of them has a maximum size that is independently less than 40 angstroms. In the embodiment, L 1A L 1B L 1C L 1D and L1E Each of them has a maximum size that is independently less than 30 angstroms. In the embodiment, L 1A L 1B L 1C L 1D and L 1E Each of them has a maximum size that is independently less than 20 angstroms. In the embodiment, L 1A L 1B L 1C L 1D and L 1E The maximum size of each of them is independently less than 10 angstroms.

[0172] In the embodiment, L 1A The maximum size is independently less than 50 angstroms. In the embodiment, L 1A The maximum size is independently less than 40 angstroms. In the embodiment, L 1A The maximum size is independently less than 30 angstroms. In the embodiment, L 1A The maximum size is independently less than 20 angstroms. In the embodiment, L 1A The maximum size is independently less than 10 angstroms.

[0173] In the embodiment, L 1B The maximum size is independently less than 50 angstroms. In the embodiment, L 1B The maximum size is independently less than 40 angstroms. In the embodiment, L 1B The maximum size is independently less than 30 angstroms. In the embodiment, L 1B The maximum size is independently less than 20 angstroms. In the embodiment, L 1B The maximum size is independently less than 10 angstroms.

[0174] In the embodiment, L 1C The maximum size is independently less than 50 angstroms. In the embodiment, L 1C The maximum size is independently less than 40 angstroms. In the embodiment, L 1C The maximum size is independently less than 30 angstroms. In the embodiment, L 1C The maximum size is independently less than 20 angstroms. In the embodiment, L 1C The maximum size is independently less than 10 angstroms.

[0175] In the embodiment, L 1D The maximum size is independently less than 50 angstroms. In the embodiment, L 1D The maximum size is independently less than 40 angstroms. In the embodiment, L 1D The maximum size is independently less than 30 angstroms. In the embodiment, L 1D The maximum size is independently less than 20 angstroms. In the embodiment, L 1DThe maximum size is independently less than 10 angstroms.

[0176] In the embodiment, L 1E The maximum size is independently less than 50 angstroms. In the embodiment, L 1E The maximum size is independently less than 40 angstroms. In the embodiment, L 1E The maximum size is independently less than 30 angstroms. In the embodiment, L 1E The maximum size is independently less than 20 angstroms. In the embodiment, L 1E The maximum size is independently less than 10 angstroms.

[0177] In this embodiment, the nucleic acid (A) is an oligonucleotide. In this embodiment, an L... 1A Linked to the 3' carbon of the oligonucleotide. In an example, an L... 1A It is linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In an example, an L 1A Linked to the 5' carbon of the oligonucleotide. In an example, an L... 1A It is linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). In an example, an L 1A Linked to the 2' carbon of the oligonucleotide. In an example, an L... 1A Linked to the nucleobases of oligonucleotides.

[0178] In an embodiment, at least one L 1A It is linked to the 3' carbon of the oligonucleotide at the 3' end. In the examples, at least one L 1A The oligonucleotide is attached to its 3' end with a 3' nitrogen atom (e.g., the 3' nitrogen atom of the morpholino group). In an example, at least one L 1A The oligonucleotide is attached to its 5' end at the 5' carbon. In an example, at least one L 1A The oligonucleotide is attached to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group) at the 5' end.

[0179] In this embodiment, the nucleic acid (A) is a double-stranded oligonucleotide. In this embodiment, an L... 1A Linked to the 3' carbon of a double-stranded oligonucleotide. In an example, an L... 1A The 3' end of the double-stranded oligonucleotide is attached to the 3' carbon of the double-stranded oligonucleotide. In an embodiment, an L 1A The 3' end of the antisense strand of the double-stranded oligonucleotide is linked to the 3' carbon of the double-stranded oligonucleotide. In an embodiment, an L 1A The 3' end of the sense strand of the double-stranded oligonucleotide is attached to the 3' carbon of the double-stranded oligonucleotide.

[0180] In the embodiment, an L 1A The 3' end of the double-stranded oligonucleotide is linked to a 3' nitrogen atom (e.g., the 3' nitrogen atom of the morpholino group). In an example, an L 1A The 3' end of the antisense strand of the double-stranded oligonucleotide is linked to the 3' nitrogen of the double-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In an example, an L 1A The 3' end of the sense strand of the double-stranded oligonucleotide is linked to the 3' nitrogen of the double-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group).

[0181] In the embodiment, an L 1A The 5' end of the double-stranded oligonucleotide is attached to the 5' carbon of the double-stranded oligonucleotide. In an embodiment, an L 1A The 5' end of the antisense strand of the double-stranded oligonucleotide is linked to the 5' carbon of the double-stranded oligonucleotide. In an embodiment, an L 1A The sense strand of the double-stranded oligonucleotide is attached to the 5' carbon at the 5' end of the sense strand.

[0182] In the embodiment, an L 1A The 5' end of the double-stranded oligonucleotide is linked to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group). In an example, an L 1A The antisense strand of the double-stranded oligonucleotide is linked to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group). In an embodiment, an L 1A The sense strand of the double-stranded oligonucleotide is attached to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group) at the 5' end.

[0183] In the embodiment, an L 1A Linked to the 2' carbon of a double-stranded oligonucleotide. In an example, an L... 1A The 2' carbon of the double-stranded oligonucleotide is attached to either of its 5' ends. In an example, an L... 1A It is connected to the 2' carbon at the 5' end of the sense chain. In an embodiment, an L 1A It is attached to the 2' carbon at the 5' end of the antisense chain. In an embodiment, an L 1A The 2' carbon of the double-stranded oligonucleotide is attached to either of its 3' ends. In an example, an L 1A It is connected to the 2' carbon at the 3' end of the sense chain. In an embodiment, an L 1A It is attached to the 2' carbon at the 3' end of the antisense chain.

[0184] In the embodiment, an L 1ALinked to the nucleobases of a double-stranded oligonucleotide. In an example, an L... 1A Linked to the nucleobases of the sense strand of the double-stranded oligonucleotide. In an example, an L... 1A Linked to the nucleobases of the antisense strand of the double-stranded oligonucleotide. In an example, an L 1A The nucleobase of the double-stranded oligonucleotide is linked at either of its 3' ends. In an example, an L... 1A The nucleobase of the double-stranded oligonucleotide is linked to the antisense strand at the 3' end. In an example, an L... 1A The nucleobase of the double-stranded oligonucleotide is linked to the sense strand at the 3' end. In an embodiment, an L 1A The nucleobase of the double-stranded oligonucleotide is linked at either 5' end. In an example, an L... 1A The nucleobase of the double-stranded oligonucleotide is linked to the antisense strand at the 5' end. In an example, an L... 1A The nucleobase of the double-stranded oligonucleotide is linked to the sense strand at the 5' end of the double-stranded oligonucleotide.

[0185] In this embodiment, the nucleic acid (A) is a single-stranded oligonucleotide. In this embodiment, an L... 1A It is linked to the 3' carbon of a single-stranded oligonucleotide at the 3' end.

[0186] In the embodiment, an L 1A The 3' end of the single-stranded oligonucleotide is linked to the 3' nitrogen of the single-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group).

[0187] In the embodiment, an L 1A It is linked to the 5' carbon of a single-stranded oligonucleotide at the 5' end.

[0188] In the embodiment, an L 1A It is attached at the 5' end to the 6' carbon of a single-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group).

[0189] In the embodiment, an L 1A Linked to the 2' carbon of a single-stranded oligonucleotide. In an example, an L... 1A An L1A is attached to the 2' carbon of the single-stranded oligonucleotide at the 5' end. In an example, an L1A is attached to the 2' carbon of the single-stranded oligonucleotide at the 3' end.

[0190] In the embodiment, an L 1A Linked to the nucleobases of a single-stranded oligonucleotide. In an example, an L... 1AIt is linked to the nucleobase of a single-stranded oligonucleotide at the 3' end. In the example, an L 1A It is linked to the nucleobase of a single-stranded oligonucleotide at the 5' end.

[0191] In the embodiment, L 1A Independently, it is -O-, -C(O)-, -C(O)O-, -OC(O)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(CH3)-O-, -OP(O)(N(CH3)2)-N-, -OP(O)(N(CH3)2)-O-, -OP(S)(N(CH3)2)-N-, -OP(S)(N(CH3)2)-O-, -P(O)(N(CH3)2)-N-, -P(O)(N(CH3)2)-O-, -P(S)(N(CH3)2)-N-, -P(S)(N(CH3)2)-O-, substituted or unsubstituted alkylene or substituted or unsubstituted heteroalkylene. In the examples, L 1A Independently, it can be -O-, -C(O)-, -C(O)O-, or -OC(O)-. In the embodiment, L 1A Independently, it can be -OPO2-O-, -OP(O)(S)-O-, -OP(O)(CH3)-O-, or -OP(S)(CH3)-O-. In the embodiment, L 1A Independently, it is -OP(O)(N(CH3)2)-N-, -OP(O)(N(CH3)2)-O-, -OP(S)(N(CH3)2)-N-, or -OP(S)(N(CH3)2)-O-. In the embodiment, L 1A Independently, it is -P(O)(N(CH3)2)-N-, -P(O)(N(CH3)2)-O-, -P(S)(N(CH3)2)-N- or -P(S)(N(CH3)2)-O-.

[0192] In the embodiment, L 1A Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 1A Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 1A Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 1A It is independently a substituted or unsubstituted C1-C2 alkylene group.

[0193] In the embodiment, L 1A Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 16-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 12-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1A Independently, it is a substituted or unsubstituted 2- to 4-membered heteroalkylene group. In the examples, L 1A It is independently a substituted or unsubstituted 2- to 3-membered heteroalkylene group.

[0194] In the embodiment, L 1A Independently In the embodiment, L 1A Independently -OPO2-O-. In the embodiment, L 1A Independently -OP(O)(S)-O-. In the embodiment, L 1A Independently -O-. In the embodiment, L 1A It is independently hydrogen-S-.

[0195] In the embodiment, L 1A It is linked to the 3' nitrogen of the morpholino group. In the examples, L 1A Independently -C(O)-. In the embodiment, L 1A It is linked to the 6' carbon of the morpholino group. In the examples, L 1A Independently, it is -OP(O)(N(CH3)2)-N-. In the embodiment, L 1A Independently -OP(O)(N(CH3)2)-O-. In the embodiment, L 1A Independently -P(O)(N(CH3)2)-N-. In the embodiment, L 1A Independently, it is -P(O)(N(CH3)2)-O-.

[0196] In the embodiment, L 1B Independently, it is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene. In the examples, L 1B Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L1B Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 1B Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 1B It is independently a substituted or unsubstituted C1-C2 alkylene group.

[0197] In the embodiment, L 1B Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 16-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 12-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 1B Independently, it is a substituted or unsubstituted 2- to 4-membered heteroalkylene group. In the examples, L 1B It is independently a substituted or unsubstituted 2- to 3-membered heteroalkylene group.

[0198] In the embodiment, L 1B Independently for -L 10 -NH-C(O)- or -L 10 -C(O)-NH-. L 10 It is a substituted or unsubstituted alkylene group.

[0199] In the embodiment, L 10 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 10 Independently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 10 Independently unsubstituted alkylene (e.g., C1-C) 20C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 10 Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 10 Independently for substituted C1-C 20 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with a hydroxyl group (OH). 20 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with hydroxymethyl. 20 Alkylene. In the examples, L 10 Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 10 Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 10 Independently for substituted C1-C 12 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with a hydroxyl group (OH). 12 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with hydroxymethyl. 12 Alkylene. In the examples, L 10 Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 10 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C8 alkylene group. In the examples, L 10 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, L 10 Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 10 Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C6 alkylene group. In the examples, L 10 Independently, it is a C1-C6 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C1-C6 alkylene group substituted with hydroxymethyl. In the examples, L 10 Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 10Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C4 alkylene group. In the examples, L 10 Independently, it is a C1-C4 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C1-C4 alkylene group substituted with hydroxymethyl. In the examples, L 10 Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 10 Independently, it is a substituted or unsubstituted C1-C2 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C2 alkylene group. In the examples, L 10 Independently, it is a C1-C2 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C1-C2 alkylene group substituted with hydroxymethyl. In the examples, L 10 It is independently an unsubstituted C1-C2 alkylene group.

[0200] In the embodiment, L 1B Independently In the embodiment, L 1B Independently .

[0201] In the embodiment, L 1B Independently , , , , , , , , , , or w1 is an integer from 0 to 10. w2 is an integer from 0 to 5. w3 is an integer from 0 to 5. w4 is an integer from 0 to 5.

[0202] In the embodiment, L 1B Independently , , , , , , , , , , or w1, w2, w3, and w4 are as described above.

[0203] In the embodiment, w1 is 0. In the embodiment, w1 is 1. In the embodiment, w1 is 2. In the embodiment, w1 is 3. In the embodiment, w1 is 4. In the embodiment, w1 is 5. In the embodiment, w1 is 6. In the embodiment, w1 is 7. In the embodiment, w1 is 8. In the embodiment, w1 is 9. In the embodiment, w1 is 10. In the embodiment, w2 is 0. In the embodiment, w2 is 1. In the embodiment, w2 is 2. In the embodiment, w2 is 3. In the embodiment, w2 is 4. In the embodiment, w2 is 5. In the embodiment, w3 is 0. In the embodiment, w3 is 1. In the embodiment, w3 is 2. In the embodiment, w3 is 3. In the embodiment, w3 is 4. In the embodiment, w3 is 5. In the embodiment, w4 is 0. In the embodiment, w4 is 1. In the embodiment, w4 is 2. In the embodiment, w4 is 3. In the embodiment, w4 is 4. In the embodiment, w4 is 5.

[0204] In the embodiment, L 1B Independently .

[0205] In the embodiment, L 1B Independently In the embodiment, L 1B Independently In one embodiment, w4 is 0. In one embodiment, w1 is 1. In one embodiment, w1 is 2. In one embodiment, w2 is 3. In one embodiment, w4 is 0 and w1 is 2. In one embodiment, w4 is 0 and w1 is 3. In one embodiment, w4 is 0 and w1 is 4.

[0206] In the embodiment, L 1B Independently In the embodiment, L 1B Independently .

[0207] In the embodiment, -L 1A -L 1B -Independently for-OL 10 -NH-C(O)- or -OL 10 -C(O)-NH-. L 10 Independently, it is a substituted or unsubstituted alkylene group, a substituted or unsubstituted heteroalkylene group, or a substituted or unsubstituted heteroenyl group. In the examples, -L 1A -L 1B -Independently for-OL 10 -NH-C(O)-. In the embodiment, -L 1A -L 1B -Independently for-OL10 -C(O)-NH-.

[0208] In the embodiment, L 10 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 10 Independently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 10 Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 10 Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 10 Independently for substituted C1-C 20 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with a hydroxyl group (OH). 20 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with hydroxymethyl. 20 Alkylene. In the examples, L 10 Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 10 Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 10 Independently for substituted C1-C 12 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with a hydroxyl group (OH). 12 Alkylene. In the examples, L 10 Independently, it is a C1-C substituted with hydroxymethyl. 12 Alkylene. In the examples, L 10 Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 10 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C8 alkylene group. In the examples, L 10 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L10 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, L 10 Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 10 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, L 10 Independently, it is a substituted C5-C8 alkylene group. In the examples, L 10 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, L 10 Independently, it is an unsubstituted C5-C8 alkylene group. In the examples, L 10 Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C6 alkylene group. In the examples, L 10 Independently, it is a C1-C6 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C1-C6 alkylene group substituted with hydroxymethyl. In the examples, L 10 Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 10 Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C4 alkylene group. In the examples, L 10 Independently, it is a C1-C4 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C1-C4 alkylene group substituted with hydroxymethyl. In the examples, L 10 Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 10 Independently, it is a substituted or unsubstituted C1-C2 alkylene group. In the examples, L 10 Independently, it is a substituted C1-C2 alkylene group. In the examples, L 10 Independently, it is a C1-C2 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C1-C2 alkylene group substituted with hydroxymethyl. In the examples, L 10 It is independently an unsubstituted C1-C2 alkylene group.

[0209] In the embodiment, -L 1A -L 1B - Independently for , or In the embodiment, -L 1A-L 1B - Independently for In the embodiment, -L 1A -L 1B - Independently for In the embodiment, -L 1A -L 1B - Independently for .

[0210] In the embodiment, -L 1A -L 1B -Independently for-OPO2-OL 10 -NH-C(O)-、-OP(O)(S)-OL 10 -NH-C(O)-、-OPO2-OL 10 -C(O)-NH- or -OP(O)(S)-OL 10 -C(O)-NH-. In the embodiment, L 10 Independently, it is a substituted or unsubstituted alkylene group. In the examples, -L 1A -L 1B -Independently for-OPO2-OL 10 -NH-C(O)- or -OP(O)(S)-OL 10 -NH-C(O)-. In the embodiment, -L 1A -L 1B -Independently for-OPO2-OL 10 -C(O)-NH- or -OP(O)(S)-OL 10 -C(O)-NH-. In the embodiment, L 10 Independently, it is a substituted or unsubstituted alkylene group. In the examples, L 10 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, L 10 Independently, it is a substituted C5-C8 alkylene group. In the examples, L 10 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L 10 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, L 10 It is independently an unsubstituted C5-C8 alkylene group.

[0211] In the embodiment, -L 1A -L 1B - Independently for , , , , , , , , , , or .

[0212] In the embodiment, -L 1A -L 1B - Independently for , , or In the embodiment, -L 1A -L 1B - Independently for or In the embodiment, -L 1A -L 1B - Independently for or In the embodiment, -L 1A -L 1B - Independently for or In the embodiment, -L 1A -L 1B - Independently for or .

[0213] In the embodiment, -L 1A -L 1B - Independently for , , or And it is linked to the 3' carbon of the oligonucleotide. In the examples, -L 1A -L 1B - Independently linked to the 3' carbon of the oligonucleotide or In the embodiment, -L 1A -L 1B - Independently linked to the 3' carbon of the oligonucleotide or .

[0214] In the embodiment, -L 1A -L 1B - Independently for or And it is linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the examples, -L 1A -L 1B - Independently linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the embodiment, -L1A -L 1B - Independently linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). .

[0215] In the embodiment, -L 1A -L 1B - Independently for , , or And it is linked to the 5' carbon of the oligonucleotide. In the examples, -L 1A -L 1B - Independently linked to the 5' carbon of the oligonucleotide or In the embodiment, -L 1A -L 1B - Independently linked to the 5' carbon of the oligonucleotide or .

[0216] In embodiments where the oligonucleotide includes a morpholino group, L 1A Independently, it is -P(O)(N(CH3)2)-N- or -P(O)(N(CH3)2)-O-. In the embodiments, L 1B It is a substituted or unsubstituted heterocyclic alkyl group. In the examples, L 1B It is a substituted heterocyclic alkyl group. In the examples, L 1B It is an unsubstituted heterocyclic alkyl group. In the examples, L 1B It is a substituted or unsubstituted piperidinylene. In the examples, L 1B It is a substituted piperidinyl group. In the examples, L 1B It is an unsubstituted piperidinyl group. In the examples, L 1B It is a substituted or unsubstituted piperazinylene. In the examples, L 1B It is a substituted piperazine group. In the examples, L 1B It is an unsubstituted piperazine group. In the examples, -L 1A -L 1B - Independently linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). or In the embodiment, -L 1A -L 1B - Independently linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). In the embodiment, -L 1A -L1B - Independently linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). .

[0217] In the embodiment, -L 1A -L 1B - Independently linked to the nucleobases of the oligonucleotide. In the examples, -L 1A -L 1B - Independently for And it is linked to the nucleobases of oligonucleotides.

[0218] In the embodiment, L 1C Independently, it is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene; L 1D Independently, it is a bond, a substituted or unsubstituted alkylene group, a substituted or unsubstituted heteroalkylene group, a substituted or unsubstituted arylene group, or a substituted or unsubstituted heteroarylene group; and L 1E Independently bonded, substituted or unsubstituted heteroalkylene or -NHC(O)-.

[0219] In the embodiment, L 1C Independently, it is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene. In the examples, L 1C Independently, it is a substituted or unsubstituted alkylene group. In the examples, L 1C Independently substituted or unsubstituted C1-C 10 Alkylene or substituted or unsubstituted 2- to 10-membered heteroalkylene. In the examples, L 1C Independently substituted or unsubstituted C1-C 10 Alkylene. In the examples, L 1C Independently for substituted C1-C 10 Alkylene. In the examples, L 1C Independent for unsubstituted C1-C 10 Alkylene. In the examples, L 1C Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1C Independently, it is a substituted C1-C8 alkylene group. In the examples, L 1C Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, L 1C Independently, it is a substituted C3-C8 alkylene group. In the examples, L 1C Independently, it is an unsubstituted C3-C8 alkylene group. In the examples, L1C Independently, it is a substituted or unsubstituted C3-C7 alkylene group. In the examples, L 1C Independently, it is a substituted C3-C7 alkylene group. In the examples, L 1C It is independently an unsubstituted C3-C7 alkylene group.

[0220] In the embodiment, L 1C Independently for R 1C Substituted or unsubstituted alkylene groups. In the examples, L 1C Independently for R 1C Substituted or unsubstituted C1-C 10 Alkylene. In the examples, L 1C Independently for R 1C Replacement C1-C 10 Alkylene. In the examples, L 1C Independent for unsubstituted C1-C 10 Alkylene. In the examples, L 1C Independently for R 1C Substituted or unsubstituted C1-C8 alkylene groups. In the examples, L 1C Independently for R 1C Substituted C1-C8 alkylene groups. In the examples, L 1C Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1C Independently for R 1C Substituted or unsubstituted C3-C8 alkylene groups. In the examples, L 1C Independently for R 1C Substituted C3-C8 alkylene groups. In the examples, L 1C Independently, it is an unsubstituted C3-C8 alkylene group. In the examples, L 1C Independently for R 1C Substituted or unsubstituted C3-C7 alkylene groups. In the examples, L 1C Independently for R 1C Substituted C3-C7 alkylene groups. In the examples, L 1C It is independently an unsubstituted C3-C7 alkylene group.

[0221] In the embodiment, L 1C Independently, it is a substituted or unsubstituted heteroalkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 2- to 10-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L1C Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted or unsubstituted 5- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is a substituted 5- to 8-membered heteroalkylene group. In the examples, L 1C Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0222] In the embodiment, L 1C Independently for R 1C Substituted or unsubstituted heteroalkylene compounds. In the examples, L 1C Independently for R 1C Substituted or unsubstituted 2- to 10-membered heteroalkylene groups. In the examples, L 1C Independently for R 1C Substituted 2- to 10-membered heteroalkylene groups. In the examples, L 1C Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1C Independently for R 1C Substituted or unsubstituted 2- to 8-membered heteroalkylene groups. In the examples, L 1C Independently for R 1C Substituted 2- to 8-membered heteroalkylene groups. In the examples, L 1C Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1C Independently for R 1C Substituted or unsubstituted 5- to 8-membered heteroalkylene groups. In the examples, L 1C Independently for R 1C Substituted 5- to 8-membered heteroalkylene groups. In the examples, L 1C Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0223] R 1C Independently, it is a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0224] In the embodiment, L 1D Independently, it is a bond, a substituted or unsubstituted alkylene group or a substituted or unsubstituted heteroalkylene group. In the examples, L 1D Independently used as a key.

[0225] In the embodiment, L 1D Independently, it is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene. In the examples, L 1D Independently, it is a substituted or unsubstituted alkylene group. In the examples, L 1D Independently substituted or unsubstituted C1-C 10 Alkylene or substituted or unsubstituted 2- to 10-membered heteroalkylene. In the examples, L 1D Independently substituted or unsubstituted C1-C 10 Alkylene. In the examples, L 1D Independently for substituted C1-C 10 Alkylene. In the examples, L 1D Independent for unsubstituted C1-C 10 Alkylene. In the examples, L 1D Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 1D Independently, it is a substituted C1-C8 alkylene group. In the examples, L 1D Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, L 1D Independently, it is a substituted C3-C8 alkylene group. In the examples, L 1D Independently, it is an unsubstituted C3-C8 alkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted C3-C7 alkylene group. In the examples, L 1D Independently, it is a substituted C3-C7 alkylene group. In the examples, L 1D It is independently an unsubstituted C3-C7 alkylene group.

[0226] In the embodiment, L 1D Independently for R 1D Substituted or unsubstituted alkylene groups. In the examples, L 1D Independently for R 1D Substituted or unsubstituted C1-C 10 Alkylene. In the examples, L 1D Independently for R 1D Replacement C1-C 10 Alkylene. In the examples, L 1D Independent for unsubstituted C1-C 10 Alkylene. In the examples, L 1D Independently for R 1DSubstituted or unsubstituted C1-C8 alkylene groups. In the examples, L 1D Independently for R 1D Substituted C1-C8 alkylene groups. In the examples, L 1D Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 1D Independently for R 1D Substituted or unsubstituted C3-C8 alkylene groups. In the examples, L 1D Independently for R 1D Substituted C3-C8 alkylene groups. In the examples, L 1D Independently, it is an unsubstituted C3-C8 alkylene group. In the examples, L 1D Independently for R 1D Substituted or unsubstituted C3-C7 alkylene groups. In the examples, L 1D Independently for R 1D Substituted C3-C7 alkylene groups. In the examples, L 1D It is independently an unsubstituted C3-C7 alkylene group.

[0227] In the embodiment, L 1D Independently, it is a substituted or unsubstituted heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 2- to 10-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted or unsubstituted 5- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is a substituted 5- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0228] In the embodiment, L 1D Independently for R 1D Substituted or unsubstituted heteroalkylene compounds. In the examples, L 1D Independently for R 1D Substituted or unsubstituted 2- to 10-membered heteroalkylene groups. In the examples, L 1D Independently for R 1DSubstituted 2- to 10-membered heteroalkylene groups. In the examples, L 1D Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1D Independently for R 1D Substituted or unsubstituted 2- to 8-membered heteroalkylene groups. In the examples, L 1D Independently for R 1D Substituted 2- to 8-membered heteroalkylene groups. In the examples, L 1D Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, via R... 1D Substituted or unsubstituted 5- to 8-membered heteroalkylene groups. In the examples, L 1D Independently for R 1D Substituted 5- to 8-membered heteroalkylene groups. In the examples, L 1D Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0229] In the embodiment, L 1D Independently, it is a substituted or unsubstituted aryl group. In the embodiments, L 1D Independently substituted or unsubstituted aryl groups (e.g., C6-C) 12 C6-C 10 Or phenyl). In the examples, L 1D Independently substituted aryl groups (e.g., C6-C) 12 C6-C 10 Or phenyl). In the examples, L 1D Independently, as unsubstituted aryl groups (e.g., C6-C) 12 C6-C 10 Or phenyl). In the examples, L 1D Independently substituted or unsubstituted C6-C 12 Arylene. In an embodiment, L 1D Independently for substituted C6-C 12 Arylene. In an embodiment, L 1D Independent for unreplaced C6-C 12 Arylene. In an embodiment, L 1D Independently substituted or unsubstituted C6-C 10 Arylene. In an embodiment, L 1D Independently for substituted C6-C 10 Arylene. In an embodiment, L 1D Independent for unreplaced C6-C 10 Arylene. In an embodiment, L 1D Independently, it is a substituted or unsubstituted phenylene. In the examples, L 1DIndependently, it is a substituted phenylene. In the examples, L 1D Independently, it is an unsubstituted phenylene. In the examples, L 1D Independently, it is a substituted or unsubstituted biphenylene. In the examples, L 1D Independently, it is a substituted biphenylene. In the examples, L 1D Independently, it is an unsubstituted biphenylene. In the examples, L 1D Independently, it is either substituted or unsubstituted naphthyl group. In the examples, L 1D Independently, it is a substituted naphthyl group. In the examples, L 1D Independently, it is an unsubstituted naphthyl group.

[0230] In the embodiment, L 1D Independently for R 1D Substituted or unsubstituted aryl groups (e.g., C6-C) 12 C6-C 10 Or phenyl). In the examples, L 1D Independently for R 1D Substituted aryl groups (e.g., C6-C) 12 C6-C 10 Or phenyl). In the examples, L 1D Independently, as unsubstituted aryl groups (e.g., C6-C) 12 C6-C 10 Or phenyl). In the examples, L 1D Independently for R 1D Substituted or unsubstituted C6-C 12 Arylene. In an embodiment, L 1D Independently for R 1D Replacement C6-C 12 Arylene. In an embodiment, L 1D Independent for unreplaced C6-C 12 Arylene. In an embodiment, L 1D Independently for R 1D Substituted or unsubstituted C6-C 10 Arylene. In an embodiment, L 1D Independently for R 1D Replacement C6-C 10 Arylene. In an embodiment, L 1D Independent for unreplaced C6-C 10 Arylene. In an embodiment, L 1D Independently for R 1D Substituted or unsubstituted phenylene oxides. In the examples, L 1D Independently for R 1DSubstituted phenylene. In the examples, L 1D Independently, it is an unsubstituted phenylene. In the examples, L 1D Independently for R 1D Substituted or unsubstituted biphenylene. In the examples, L 1D Independently for R 1D Substituted biphenylene. In the examples, L 1D Independently, it is an unsubstituted biphenylene. In the examples, L 1D Independently for R 1D Substituted or unsubstituted naphthyl group. In the examples, L 1D Independently for R 1D Substituted naphthyl group. In the examples, L 1D Independently, it is an unsubstituted naphthyl group.

[0231] In the embodiment, L 1D Independently, it is a substituted or unsubstituted heteroaryl group. In the examples, L 1D Independently, it is a substituted heteroaryl group. In the examples, L 1D Independently, it is an unsubstituted heteroaryl group. In the examples, L 1D Independently, it is a substituted or unsubstituted heteroaryl group (e.g., 5 to 12, 5 to 10, 5 to 9, or 5 to 6). In the examples, L 1D Independently, it is a substituted heteroaryl group (e.g., 5 to 12 ternary, 5 to 10 ternary, 5 to 9 ternary, or 5 to 6 ternary). In the examples, L 1D Independently, it is an unsubstituted heteroaryl group (e.g., 5 to 12, 5 to 10, 5 to 9, or 5 to 6). In the examples, L 1D Independently, it is a substituted or unsubstituted 5- to 12-membered heteroaryl group. In the examples, L 1D Independently, it is a substituted 5- to 12-membered heteroaryl group. In the examples, L 1D Independently, it is an unsubstituted 5- to 12-membered heteroaryl group. In the examples, L 1D Independently, it is a substituted or unsubstituted 5- to 10-membered heteroaryl group. In the examples, L 1D Independently, it is a substituted 5- to 10-membered heteroaryl group. In the examples, L 1D Independently, it is an unsubstituted 5- to 10-membered heteroaryl group. In the examples, L 1D Independently, it is a substituted or unsubstituted 5- to 9-membered heteroaryl group. In the examples, L 1D Independently substituted 5- to 9-membered heteroaryl groups. In the examples, L 1D Independently, it is an unsubstituted 5- to 9-membered heteroaryl group. In the examples, L 1DIndependently, it is a substituted or unsubstituted 5- to 6-membered heteroaryl group. In the examples, L 1D Independently, it is a substituted 5- to 6-membered heteroaryl group. In the examples, L 1D Independently, it is an unsubstituted 5 to 6-membered heteroaryl group.

[0232] R 1D Independently, it is a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0233] In the embodiment, L 1E Independently, it is a bond, substituted or unsubstituted, 2 to 10-membered heteroalkylene or -NHC(O)-. In the examples, L 1E Independently used as a key. In the embodiment, L 1E Independently -NHC(O)-.

[0234] In the embodiment, L 1E Independently, it is a substituted or unsubstituted heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 2- to 10-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted or unsubstituted 5- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is a substituted 5- to 8-membered heteroalkylene group. In the examples, L 1E Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0235] In the embodiment, L 1E Independently for R 1E Substituted or unsubstituted heteroalkylene compounds. In the examples, L 1E Independently for R 1E Substituted or unsubstituted 2- to 10-membered heteroalkylene groups. In the examples, L 1E Independently for R 1E Substituted 2- to 10-membered heteroalkylene groups. In the examples, L 1EIndependently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 1E Independently for R 1E Substituted or unsubstituted 2- to 8-membered heteroalkylene groups. In the examples, L 1E Independently for R 1E Substituted 2- to 8-membered heteroalkylene groups. In the examples, L 1E Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 1E Independently for R 1E Substituted or unsubstituted 5- to 8-membered heteroalkylene groups. In the examples, L 1E Independently for R 1E Substituted 5- to 8-membered heteroalkylene groups. In the examples, L 1E Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0236] R 1E Independently, it is a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0237] In the embodiment, L 1C Independently for R 1C Substituted or unsubstituted C1-C7 alkylene or via R 1C Substituted or unsubstituted 5- to 8-membered heteroalkylene groups; L 1D Independently for the key, via R 1D Substituted or unsubstituted C1-C7 alkylene or via R 1D Substituted or unsubstituted 5- to 8-membered heteroalkylene compounds; and L 1E Independently for the key, via R 1E Substituted or unsubstituted 5 to 8 heteroalkylene groups or -NHC(O)-.

[0238] In the embodiment, L 1C Independently for R 1C Substituted or unsubstituted C1-C7 alkylene groups. In the examples, L 1C Independently for R 1C Substituted or unsubstituted 5- to 8-membered heteroalkylene groups. In the examples, L 1D Independently used as a key. In the embodiment, L 1D Independently for R 1D Substituted or unsubstituted C1-C7 alkylene groups. In the examples, L 1E Independently used as a key. In the embodiment, L 1E Independently for R 1ESubstituted or unsubstituted 5- to 8-membered heteroalkylene groups. In the examples, L 1E Independently -NHC(O)-.

[0239] In the embodiment, R 1C Independently oxygen or -L 8C -L 2C -R 8C In the embodiment, R 1C Independently, it is an oxygen-based compound. In the examples, R... 1C Independently for -L 8C -L 2C -R 8C L 8C Independently, it is a bonded, substituted or unsubstituted C1-C6 alkylene or a substituted or unsubstituted 2- to 6-membered heteroalkylene. L 8C Independently, it is a bonded, substituted or unsubstituted C1-C6 alkylene or a substituted or unsubstituted 2- to 6-membered heteroalkylene. L 2C Independently bonded or unsubstituted alkylene groups. R 8C Independently hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl.

[0240] In the embodiment, R 1D Independently oxygen or -L 8D -L 2D -R 8D In the embodiment, R 1D Independently, it is an oxygen-based compound. In the examples, R... 1D Independently for -L 8D -L 2D -R 8D L 8D Independently, it is a bonded, substituted or unsubstituted C1-C6 alkylene or a substituted or unsubstituted 2- to 6-membered heteroalkylene. L 8D Independently, it is a bonded, substituted or unsubstituted C1-C6 alkylene or a substituted or unsubstituted 2- to 6-membered heteroalkylene. L 2D Independently bonded or unsubstituted alkylene groups. R 8D Independently hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl.

[0241] In the embodiment, R 1E Independently oxygen or -L 8E -L 2E -R 8E In the embodiment, R 1E Independently, it is an oxygen-based compound. In the examples, R... 1E Independently for -L 8E -L2E -R 8E L 8E Independently, it is a bonded, substituted or unsubstituted C1-C6 alkylene or a substituted or unsubstituted 2- to 6-membered heteroalkylene. L 8E Independently, it is a bonded, substituted or unsubstituted C1-C6 alkylene or a substituted or unsubstituted 2- to 6-membered heteroalkylene. L 2E Independently bonded or unsubstituted alkylene groups. R 8E Independently hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl.

[0242] In the embodiments, the half-life extended motif has the following structure: (III-a). L 8A Independently, it is a bond, a substituted or unsubstituted alkylene group or a substituted or unsubstituted heteroalkylene group. L 2A Independently bonded or unsubstituted alkylene groups. L 1A L 1B L 1C L 1D L 1E L 2C L 8C and R 8C As described above.

[0243] In the embodiments, the half-life extended motif has the following structure: (III-b). L 1A L 1B L 1C L 1D L 1E L 2A L 2D L 8A L 8D and R 8D As described above.

[0244] In the embodiments, the half-life extended motif has the following structure: (III-c). L 1A L 1B L 1C L 1D L 1E L 2A L 2E L 8A L 8E and R 8E As described above.

[0245] In the embodiments, the half-life extended motif has the following structure: (III-d). L 1A L 1B L 1C L 1D L 1E L 2A L 2C L 2D L 8A L 8C L 8D R 8C and R 8D As described above.

[0246] In the embodiments, the half-life extended motif has the following structure: (III-e). L 1A L 1B L 1C L 1D L 1E L 2A L 2D L 2E L 8A L 8D L 8E R 8D and R 8E As described above.

[0247] In the embodiments, the half-life extended motif has the following structure: (III-f). L 1A L 1B L 1C L 1D L 1E L 2A L 2C L 2E L 8A L 8C L 8E R 8C and R 8E As described above.

[0248] In the embodiments, the half-life extended motif has the following structure: (III-g). L 1A L 1B L 1C L 1D L 1E L 2A L 2CL 2D L 2E L 8A L 8C L 8D L 2E R 8C R 8D and R 8E As described above.

[0249] In the embodiment, L 8A Independently used as a key. In the embodiment, L 8A Independently, it is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene. In the examples, L 8A Independently, it is a substituted or unsubstituted alkylene group. In the examples, L 8A Independently substituted or unsubstituted C1-C 10 Alkylene or substituted or unsubstituted 2- to 10-membered heteroalkylene. In the examples, L 8A Independently substituted or unsubstituted C1-C 10 Alkylene. In the examples, L 8A Independently for substituted C1-C 10 Alkylene. In the examples, L 8A Independent for unsubstituted C1-C 10 Alkylene. In the examples, L 8A Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 8A Independently, it is a substituted C1-C8 alkylene group. In the examples, L 8A Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 8A Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, L 8A Independently, it is a substituted C3-C8 alkylene group. In the examples, L 8A Independently, it is an unsubstituted C3-C8 alkylene group. In the examples, L 8A Independently, it is a substituted or unsubstituted C3-C7 alkylene group. In the examples, L 8A Independently, it is a substituted C3-C7 alkylene group. In the examples, L 8A It is independently an unsubstituted C3-C7 alkylene group.

[0250] In the embodiment, L 8A Independently for R 8A Substituted or unsubstituted alkylene groups. In the examples, L 8A Independently for R 8A Substituted or unsubstituted C1-C10 Alkylene. In the examples, L 8A Independently for R 8A Replacement C1-C 10 Alkylene. In the examples, L 8A Independent for unsubstituted C1-C 10 Alkylene. In the examples, L 8A Independently for R 8A Substituted or unsubstituted C1-C8 alkylene groups. In the examples, L 8A Independently, it is a C1-C8 alkylene group substituted with R8A. In the examples, L 8A Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 8A Independently for R 8A Substituted or unsubstituted C3-C8 alkylene groups. In the examples, L 8A Independently, it is a C3-C8 alkylene group substituted with R8A. In the examples, L 8A Independently, it is an unsubstituted C3-C8 alkylene group. In the examples, L 8A Independently for R 8A Substituted or unsubstituted C3-C7 alkylene groups. In the examples, L 8A Independently, it is a C3-C7 alkylene group substituted with R8A. In the examples, L 8A It is independently an unsubstituted C3-C7 alkylene group.

[0251] In the embodiment, L 8A Independently, it is a substituted or unsubstituted heteroalkylene group. In the examples, L 8A Independently, it is a substituted or unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 8A Independently, it is a substituted 2- to 10-membered heteroalkylene group. In the examples, L 8A Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 8A Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 8A Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 8A Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 8A Independently, it is a substituted or unsubstituted 5- to 8-membered heteroalkylene group. In the examples, L 8A Independently, it is a substituted 5- to 8-membered heteroalkylene group. In the examples, L 8A Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0252] In the embodiment, L 8AIndependently for R 8A Substituted or unsubstituted heteroalkylene compounds. In the examples, L 8A Independently for R 8A Substituted or unsubstituted 2- to 10-membered heteroalkylene groups. In the examples, L 8A Independently for R 8A Substituted 2- to 10-membered heteroalkylene groups. In the examples, L 8A Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 8A Independently for R 8A Substituted or unsubstituted 2- to 8-membered heteroalkylene groups. In the examples, L 8A Independently for R 8A Substituted 2- to 8-membered heteroalkylene groups. In the examples, L 8A Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, via R... 8A Substituted or unsubstituted 5- to 8-membered heteroalkylene groups. In the examples, L 8A Independently for R 8A Substituted 5- to 8-membered heteroalkylene groups. In the examples, L 8A Independently, it is an unsubstituted 5 to 8-membered heteroalkylene group.

[0253] In the embodiment, L 2A Independent for unsubstituted C2-C 24 Alkylene. In the examples, L 2A Independent for unsubstituted C2-C 22 Alkylene. In the examples, L 2A Independent for unreplaced C5-C 22 Alkylene. In the examples, L 2A Independently for unreplaced C 10 -C 22 Alkylene. In the examples, L 2A Independently for unreplaced C 12 -C 22 Alkylene. In the examples, L 2A Independently for unreplaced C 10 -C 20 Alkylene. In the examples, L 2A Independently for unreplaced C 12 -C 20 Alkylene. In the examples, L 2A Independently for unreplaced C 10 -C 18 Alkylene. In the examples, L 2A Independently for unreplaced C 12 -C 18Alkylene. In the examples, L 2A Independently for unreplaced C 10 -C 16 Alkylene. In the examples, L 2A Independently for unreplaced C 12 -C 16 Alkylene. In the examples, L 2A Independently for unreplaced C 14 -C 16 Alkylene. In the examples, L 2A Independently for unreplaced C 14 -C 15 Alkylene. In the examples, L 2A Independently for unreplaced C 14 Alkylene. In the examples, L 2A Independently for unreplaced C 15 Alkylene. In the examples, L 2A Independently for unreplaced C 16 Alkylene.

[0254] In the embodiment, L 2A Independently for unsubstituted, unbranched C2-C 24 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C2-C 22 Alkylene. In the examples, L 2A Independent for unsubstituted, unbranched C5-C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 10 -C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 12 -C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 10 -C 20 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 12 -C 20 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 10 -C 18 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 12 -C 18 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C10 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 12 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 14 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 14 -C 15 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 14 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 15 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched C 16 Alkylene.

[0255] In the embodiment, L 2A Independently for unsubstituted, unbranched saturated C2-C 24 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C2-C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C5-C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 10 -C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 12 -C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 10 -C 20 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 12 -C 20 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 10 -C 18 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 12 -C 18 Alkylene. In the examples, L 2AIndependently for unsubstituted, unbranched saturated C 10 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 12 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 14 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 14 -C 15 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 14 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 15 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched saturated C 16 Alkylene.

[0256] In the embodiment, L 2A Independently unsubstituted, unbranched, unsaturated C2-C 24 Alkylene. In the examples, L 2A Independently unsubstituted, unbranched, unsaturated C2-C 22 Alkylene. In the examples, L 2A Independently unsubstituted, unbranched, unsaturated C5-C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 10 -C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 12 -C 22 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 10 -C 20 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 12 -C 20 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 10 -C 18 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 12 -C 18Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 10 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 12 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 14 -C 16 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 14 -C 15 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 14 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 15 Alkylene. In the examples, L 2A Independently for unsubstituted, unbranched, unsaturated C 16 Alkylene. In the examples, L 8A Independently as a key, and L 2A Independent for unsubstituted C2-C 22 Alkylene.

[0257] In the embodiment, L 2A Independently as a key, and L 8A Independent for unsubstituted C2-C 22 Alkylene.

[0258] In the embodiment, L 8A Independent for unsubstituted C2-C 24 Alkylene. In the examples, L 8A Independent for unsubstituted C2-C 22 Alkylene. In the examples, L 8A Independent for unreplaced C5-C 22 Alkylene. In the examples, L 8A Independently for unreplaced C 10 -C 22 Alkylene. In the examples, L 8A Independently for unreplaced C 12 -C 22 Alkylene. In the examples, L 8A Independently for unreplaced C 10 -C 20 Alkylene. In the examples, L 8A Independently for unreplaced C12 -C 20 Alkylene. In the examples, L 8A Independently for unreplaced C 10 -C 18 Alkylene. In the examples, L 8A Independently for unreplaced C 12 -C 18 Alkylene. In the examples, L 8A Independently for unreplaced C 10 -C 16 Alkylene. In the examples, L 8A Independently for unreplaced C 12 -C 16 Alkylene. In the examples, L 8A Independently for unreplaced C 14 -C 16 Alkylene. In the examples, L 8A Independently for unreplaced C 14 -C 15 Alkylene. In the examples, L 8A Independently for unreplaced C 14 Alkylene. In the examples, L 8A Independently for unreplaced C 15 Alkylene. In the examples, L 8A Independently for unreplaced C 16 Alkylene.

[0259] In the embodiment, L 8A Independently for unsubstituted, unbranched C2-C 24 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C2-C 22 Alkylene. In the examples, L 8A Independent for unsubstituted, unbranched C5-C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 10 -C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 12 -C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 10 -C 20 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 12 -C 20 Alkylene. In the examples, L8A Independently for unsubstituted, unbranched C 10 -C 18 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 12 -C 18 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 10 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 12 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 14 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 14 -C 15 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 14 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 15 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched C 16 Alkylene.

[0260] In the embodiment, L 8A Independently for unsubstituted, unbranched saturated C2-C 24 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C2-C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C5-C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 10 -C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 12 -C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 10 -C 20 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 12 -C 20 Alkylene. In the examples, L8A Independently for unsubstituted, unbranched saturated C 10 -C 18 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 12 -C 18 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 10 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 12 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 14 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 14 -C 15 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 14 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 15 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched saturated C 16 Alkylene.

[0261] In the embodiment, L 8A Independently unsubstituted, unbranched, unsaturated C2-C 24 Alkylene. In the examples, L 8A Independently unsubstituted, unbranched, unsaturated C2-C 22 Alkylene. In the examples, L 8A Independently unsubstituted, unbranched, unsaturated C5-C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 10 -C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 12 -C 22 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 10 -C 20 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 12 -C20 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 10 -C 18 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 12 -C 18 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 10 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 12 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 14 -C 16 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 14 -C 15 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 14 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 15 Alkylene. In the examples, L 8A Independently for unsubstituted, unbranched, unsaturated C 16 Alkylene.

[0262] In the embodiment, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independent of the bond or unsubstituted C2-C 22 Alkylene; and R 8C Independently, it is hydrogen, C1-C3 alkyl, or -COOH. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C In the embodiment, L 2C Independent of the bond or unsubstituted C2-C 22 Alkylene. In the examples, L 2C Independently used as a key. In the embodiment, L 2C Independent for unsubstituted C2-C 22 Alkylene. In the examples, R 8C Independently, it is hydrogen, C1-C3 alkyl, or -COOH. In the examples, R 8CIndependently hydrogen. In the examples, R 8C Independently, it is a C1-C3 alkyl group. In the examples, R 8C Independently, it is -COOH.

[0263] In the embodiment, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently as a key, and R 8C Independently, it is a C1-C3 alkyl group. In the examples, R 1C Independently -NHC(O)-CH3. In the embodiments, R 1C Independently -NHC(O)-CH2CH3. In the examples, R 1C Independently -NHC(O)-CH(CH3)2. In the examples, R 1C It is independently -NHC(O)-CH2CH2CH3.

[0264] In the embodiment, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently for unreplaced C 10 -C 22 Alkylene, and R 8C Independently -COOH. In the examples, R 1C Independently -NHC(O)-L 2C -COOH.

[0265] In the embodiment, L 2C Independently for unsubstituted, unbranched C2-C 24 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C2-C 22 Alkylene. In the examples, L 2C Independent for unsubstituted, unbranched C5-C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 10 -C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 12 -C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 10 -C 20 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C12 -C 20 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 10 -C 18 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 12 -C 18 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 10 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 12 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 14 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 14 -C 15 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 14 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 15 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched C 16 Alkylene.

[0266] In the embodiment, L 2C Independently for unsubstituted, unbranched saturated C2-C 24 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C2-C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C5-C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 10 -C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 12 -C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 10 -C 20 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C12 -C 20 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 10 -C 18 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 12 -C 18 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 10 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 12 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 14 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 14 -C 15 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 14 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 15 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched saturated C 16 Alkylene.

[0267] In the embodiment, L 2C Independently unsubstituted, unbranched, unsaturated C2-C 24 Alkylene. In the examples, L 2C Independently unsubstituted, unbranched, unsaturated C2-C 22 Alkylene. In the examples, L 2C Independently unsubstituted, unbranched, unsaturated C5-C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 10 -C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 12 -C 22 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 10 -C 20 Alkylene. In the examples, L2C Independently for unsubstituted, unbranched, unsaturated C 12 -C 20 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 10 -C 18 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 12 -C 18 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 10 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 12 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 14 -C 16 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 14 -C 15 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 14 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 15 Alkylene. In the examples, L 2C Independently for unsubstituted, unbranched, unsaturated C 16 Alkylene.

[0268] In the embodiment, R 1D Independently -NHC(O)-L 2D -R 8D L 2D Independent of the bond or unsubstituted C2-C 22 Alkylene; and R 8D Independently, it is hydrogen, C1-C3 alkyl, or -COOH. In the examples, R 1D Independently -NHC(O)-L 2D -R 8D In the embodiment, L 2D Independent of the bond or unsubstituted C2-C 22 Alkylene. In the examples, L 2D Independently used as a key. In the embodiment, L 2D Independent for unsubstituted C2-C 22 Alkylene. In the examples, R8D Independently, it is hydrogen, C1-C3 alkyl, or -COOH. In the examples, R 8D Independently hydrogen. In the examples, R 8D Independently, it is a C1-C3 alkyl group. In the examples, R 8D Independently, it is -COOH.

[0269] In the embodiment, R 1D Independently -NHC(O)-L 2D -R 8D L 2D Independently as a key, and R 8D Independently, it is a C1-C3 alkyl group. In the examples, R 1D Independently -NHC(O)-CH3. In the embodiments, R 1D Independently -NHC(O)-CH 2D H3. In the embodiment, R 1D Independently -NHC(O)-CH(CH3)2. In the examples, R 1D Independently -NHC(O)-CH 2D H 2D H3.

[0270] In the embodiment, R 1D Independently -NHC(O)-L 2D -R 8D L 2D Independently for unreplaced C 10 -C 22 Alkylene, and R 8D Independently -COOH. In the examples, R 1D Independently -NHC(O)-L 2D -COOH.

[0271] In the embodiment, L 2D Independently for unsubstituted, unbranched C2-C 24 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C2-C 22 Alkylene. In the examples, L 2D Independent for unsubstituted, unbranched C5-C 22 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 10 -C 22 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 12 -C 22 Alkylene. In the examples, L 2DIndependently for unsubstituted, unbranched C 10 -C 20 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 12 -C 20 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 10 -C 18 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 12 -C 18 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 10 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 12 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 14 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 14 -C 15 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 14 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 15 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched C 16 Alkylene.

[0272] In the embodiment, L 2D Independently for unsubstituted, unbranched saturated C2-C 24 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C2-C 22 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C5-C 22 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 10 -C 22 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 12 -C 22 Alkylene. In the examples, L 2DIndependently for unsubstituted, unbranched saturated C 10 -C 20 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 12 -C 20 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 10 -C 18 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 12 -C 18 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 10 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 12 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 14 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 14 -C 15 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 14 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 15 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched saturated C 16 Alkylene.

[0273] In the embodiment, L 2D Independently unsubstituted, unbranched, unsaturated C2-C 24 Alkylene. In the examples, L 2D Independently unsubstituted, unbranched, unsaturated C2-C 22 Alkylene. In the examples, L 2D Independently unsubstituted, unbranched, unsaturated C5-C 22 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 10 -C 22 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 12 -C 22Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 10 -C 20 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 12 -C 20 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 10 -C 18 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 12 -C 18 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 10 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 12 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 14 -C 16 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 14 -C 15 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 14 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 15 Alkylene. In the examples, L 2D Independently for unsubstituted, unbranched, unsaturated C 16 Alkylene.

[0274] In the embodiment, R 1E Independently -NHC(O)-L 2E -R 8E L 2E Independent of the bond or unsubstituted C2-C 22 Alkylene; and R 8E Independently, it is hydrogen, C1-C3 alkyl, or -COOH. In the examples, R 1E Independently -NHC(O)-L 2E -R 8E In the embodiment, L 2E Independent of the bond or unsubstituted C2-C 22 Alkylene. In the examples, L2E Independently used as a key. In the embodiment, L 2E Independent for unsubstituted C2-C 22 Alkylene. In the examples, R 8E Independently, it is hydrogen, C1-C3 alkyl, or -COOH. In the examples, R 8E Independently hydrogen. In the examples, R 8E Independently, it is a C1-C3 alkyl group. In the examples, R 8E Independently, it is -COOH.

[0275] In the embodiment, R 1E Independently -NHC(O)-L 2E -R 8E L 2E Independently as a key, and R 8E Independently, it is a C1-C3 alkyl group. In the examples, R 1E Independently -NHC(O)-CH3. In the embodiments, R 1E Independently -NHC(O)-CH 2E H3. In the embodiment, R 1E Independently -NHC(O)-CH(CH3)2. In the examples, R 1E Independently -NHC(O)-CH 2E H 2E H3.

[0276] In the embodiment, R 1E Independently -NHC(O)-L 2E -R 8E L 2E Independently for unreplaced C 10 -C 22 Alkylene, and R 8E Independently -COOH. In the examples, R 1E Independently -NHC(O)-L 2E -COOH.

[0277] In the embodiment, L 2E Independently for unsubstituted, unbranched C2-C 24 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C2-C 22 Alkylene. In the examples, L 2E Independent for unsubstituted, unbranched C5-C 22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 10 -C 22 Alkylene. In the examples, L2E Independently for unsubstituted, unbranched C 12 -C 22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 10 -C 20 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 12 -C 20 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 10 -C 18 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 12 -C 18 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 10 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 12 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 14 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 14 -C 15 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 14 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 15 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched C 16 Alkylene.

[0278] In the embodiment, L 2E Independently for unsubstituted, unbranched saturated C2-C 24 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C2-C 22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C5-C 22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 10 -C 22 Alkylene. In the examples, L2E Independently for unsubstituted, unbranched saturated C 12 -C 22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 10 -C 20 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 12 -C 20 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 10 -C 18 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 12 -C 18 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 10 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 12 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 14 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 14 -C 15 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 14 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 15 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched saturated C 16 Alkylene.

[0279] In the embodiment, L 2E Independently unsubstituted, unbranched, unsaturated C2-C 24 Alkylene. In the examples, L 2E Independently unsubstituted, unbranched, unsaturated C2-C 22 Alkylene. In the examples, L 2E Independently unsubstituted, unbranched, unsaturated C5-C 22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 10 -C22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 12 -C 22 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 10 -C 20 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 12 -C 20 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 10 -C 18 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 12 -C 18 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 10 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 12 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 14 -C 16 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 14 -C 15 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 14 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 15 Alkylene. In the examples, L 2E Independently for unsubstituted, unbranched, unsaturated C 16 Alkylene.

[0280] In the embodiment, L 1C Independently for R 1C Substituted or unsubstituted 5- to 8-membered heteroalkylene groups, L 1D Independently for the key or via R 1D Substituted or unsubstituted 5- to 8-membered heteroalkylene groups, and L 1E Independently for R 1E Substituted or unsubstituted 5- to 8-membered heteroalkylene groups or -NHC(O)-. In the examples, each R1C R 1D or R 1E It can be an oxygen group or -COOH on its own.

[0281] In the embodiment, L 1C Independently, it is an unsubstituted 5- to 8-membered heteroalkylene group. In the examples, L 1D Independently, it is a 5- to 8-membered heteroalkylene group, either oxy-substituted or unsubstituted. In the examples, L 1E Independently for R 1E Substituted or unsubstituted 5- to 8-membered heteroalkylene groups, wherein R 1E Independently, it is an oxygen-based compound or -COOH. In the examples, L 1C Independently, it is an unsubstituted 5- to 8-membered heteroalkylene group. In the examples, L 1D Independently used as a key. In the embodiment, L 1E Independently -NHC(O)-. In the embodiments, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form .

[0282] In the embodiment, L 1C Independently for R 1C Substituted C2-C5 alkyl groups; L 1D Independently, it is an unsubstituted phenylene or an unsubstituted biphenylene; L 1E Independently for R 1E Substituted or unsubstituted 5- to 8-membered heteroalkylene groups or -NHC(O)-; R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently as a key or unreplaced C 10 -C 22 Alkylene; R 8C Independently, it is an unsubstituted C1-C3 alkyl group or -COOH; and R 1E It is an oxygen atom.

[0283] In the embodiment, L 1C Independently for R 1C Substituted ethylene. In the examples, L 1D Independently, it is an unsubstituted biphenylene. In the examples, L 1E Independently -NHC(O)-. In the embodiments, R 1CIndependently -NHC(O)-L 2C -R 8C And L 2C Independently as a key, or R 8C Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 1C Independently -NHC(O)-CH3. In the embodiments, R 1C Independently -NHC(O)-CH2CH3. In the examples, R 1C Independently -NHC(O)-CH(CH3)2. In the examples, R 1C Independently, it is -NHC(O)-CH2CH2CH3. In the examples, R 1C Independently -NHC(O)-L 2C -COOH. In the examples, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form .

[0284] In the embodiment, L 1C Independently for R 1C Substituted ethylene. In the examples, L 1D Independently, it is an unsubstituted phenylene. In the examples, L 1E Independently for R 1E Substituted or unsubstituted 5- to 8-membered heteroalkylene groups. In the examples, L 1E Independently, it is a 5- to 8-membered heteroalkylene group, either oxy-substituted or unsubstituted. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C And L 2C Independently as a key, or R 8C Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 1C Independently -NHC(O)-CH3. In the embodiments, R 1C Independently -NHC(O)-CH2CH3. In the examples, R1C Independently -NHC(O)-CH(CH3)2. In the examples, R 1C Independently, it is -NHC(O)-CH2CH2CH3. In the examples, R 1C Independently -NHC(O)-L 2C -COOH. In the examples, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form .

[0285] In the embodiment, L 1C Independently for R 1C Substituted or unsubstituted ethylene or n-pentene, L 1D L is an independent key. 1E Independently -NHC(O)-, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently as a key or unreplaced C 10 -C 22 Alkylene, and R 8C It is independently an unsubstituted C1-C3 alkyl or -COOH.

[0286] In the embodiment, L 1C Independently for R 1C Substituted n-pentanediol. In the embodiments, L 1C Independently, it is an unsubstituted n-pentanediol. In the examples, L 1D Independently used as a key. In the embodiment, L 1E Independently -NHC(O)-. In the embodiments, R 1C Independently -NHC(O)-L 2C -R 8C And L 2C Independently as a key, and R 8C Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 1CIndependently -NHC(O)-CH3. In the embodiments, R 1C Independently -NHC(O)-CH2CH3. In the examples, R 1C Independently -NHC(O)-CH(CH3)2. In the examples, R 1C Independently, it is -NHC(O)-CH2CH2CH3. In the examples, R 1C Independently -NHC(O)-L 2C -COOH. In the examples, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form .

[0287] In the embodiment, L 1C Independently for R 1C Substituted ethylene. In the examples, L 1D Independently used as a key. In the embodiment, L 1E Independently -NHC(O)-. In the embodiments, R 1C Independently -NHC(O)-L 2C -R 8C And L 2C Independently as a key, and R 8C Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 1C Independently -NHC(O)-CH3. In the embodiments, R 1C Independently -NHC(O)-CH2CH3. In the examples, R 1C Independently -NHC(O)-CH(CH3)2. In the examples, R 1C Independently, it is -NHC(O)-CH2CH2CH3. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently for unreplaced C 10 -C 22 Alkylene, and R 8C Independently -COOH. In the examples, R 1C Independently -NHC(O)-L 2C-COOH. In the examples, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form .

[0288] In the embodiment, L 1C Independently for R 1C Substituted or unsubstituted n-pentylene, L 1D Independently, it is a 5- to 8-membered heteroalkylene group, either oxy-substituted or unsubstituted, L 1E Independently -NHC(O)-, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently as a key or unreplaced C 10 -C 22 Alkylene, and R 8C It is independently an unsubstituted C1-C3 alkyl or -COOH.

[0289] In the embodiment, L 1C Independently for R 1C Substituted n-pentanediol. In the embodiments, L 1D Independently, it is a 5- to 8-membered heteroalkylene group, either oxy-substituted or unsubstituted. In the examples, L 1E Independently -NHC(O)-. In the embodiments, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently as a key, and R 8C Independently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 1C Independently -NHC(O)-CH3. In the embodiments, R 1C Independently -NHC(O)-CH2CH3. In the examples, R 1C Independently -NHC(O)-CH(CH3)2. In the examples, R 1C Independently, it is -NHC(O)-CH2CH2CH3. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently for unreplaced C 10 -C 22 Alkylene, and R 8CIndependently, it is an unsubstituted C1-C3 alkyl group. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently for unreplaced C 10 -C 22 Alkylene, and R 8C Independently, it is an unsubstituted methyl group. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently for unreplaced C 10 -C 22 Alkylene, and R 8C Independently, it is an unsubstituted ethyl group. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently for unreplaced C 10 -C 22 Alkylene, and R 8C Independently -COOH. In the examples, R 1C Independently -NHC(O)-L 2C -COOH. In the examples, R 1C Independently -NHC(O)-L 2C -R 8C L 2C Independently for unreplaced C 10 -C 22 Alkylene, and R 8C Independently -COOH. In the examples, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form .

[0290] In the embodiment, L 1C Independently for R 1C Substituted methylene, L 1D L is an independent key. 1E Independently -NHC(O)-, R 1C Independently for -L 8C -L 2C -R 8C L 8C Independently, it is an unsubstituted C1-C6 alkylene or an oxy-substituted 2- to 12-membered heteroalkylene, L 2C Independently as a key, and R 8C Independently, it is an unsubstituted C1-C6 alkyl or a 2 to 12 heteroalkyl group substituted with an oxygen.

[0291] In the embodiment, L 1C Independently for R 1C Substituted methylene. In the examples, L 1D Independently used as a key. In the embodiment, L 1E Independently -NHC(O)-. In the embodiments, R 1C Independently for -L 8C -L 2C -R 8C In the embodiment, L 8C Independently, it is an unsubstituted C1-C6 alkylene group or an oxy-substituted 2- to 12-membered heteroalkylene group. In the examples, L 8C Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 8C Independently, it is a 2- to 12-membered heteroalkylene group substituted with an oxygen. In the examples, R 8C Independently, it is an unsubstituted C1-C6 alkyl group. In the examples, R 8C Independently, it is a 2- to 12-membered heteroalkyl group substituted with an oxygen. In the examples, L 8C Independently, it is an unsubstituted C1-C6 alkylene group, L 2C As the key, and R 8C Independently, it is a 2- to 12-membered heteroalkyl group substituted with an oxygen. In the examples, L 8C Independently, it is an unsubstituted C4 alkylene group, L 2C As the key, and R 8C Independently, it is a 2- to 5-membered heteroalkyl group substituted with an oxygen group. In the examples, L 8C Independently, it is an unsubstituted C4 alkylene group, L 2C As the key, and R 8C Independently substituted with hydroxyl group and substituted with C1-C 20 Alkyl-substituted 2- to 12-membered heteroalkyl groups. In the examples, L8C Independently, it is an unsubstituted C1-C6 alkylene group, L 2C As the key, and R 8C Independently hydroxyl and C1-C 15 Alkyl-substituted 2- to 12-membered heteroalkyl groups. In the examples, L 8C Independently, it is an unsubstituted C4 alkylene group, L 2C As the key, and R 8C Independently hydroxyl and C 14 -C 15 Alkyl-substituted 2- to 12-membered heteroalkyl groups. In the examples, L 8C Independently alkyl groups of 2 to 12 members substituted with oxygen, L 2C As the key, R 8C Independently, it is a 2- to 12-membered heteroalkyl group substituted with an oxygen. In the examples, L 8C Independently alkyl groups of 2 to 12 members substituted with oxygen, L 2C As the key, R 8C Independently hydroxyl and C1-C 15 Alkyl-substituted 2- to 12-membered heteroalkyl groups. In the examples, L 8C Independently alkyl groups of 2 to 12 members substituted with oxygen, L 2C As the key, R 8C Independently hydroxyl and C 14 -C 15 Alkyl-substituted 2- to 12-membered heteroalkyl groups. In the examples, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form In the embodiment, -L 1C -L 1D -L 1E -can form .

[0292] In the embodiment, L 1 for , , , , , , , , , , , , , , , , , , , , or .

[0293] In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In this embodiment, L1 is independently... In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1 Independently In the embodiment, L 1Independently In the embodiment, L 1 Independently .

[0294] In the embodiment, L 1 for , , , , or In the embodiment, L 1 for In the embodiment, L 1 for In the embodiment, L 1 for In the embodiment, L 1 for In the embodiment, L 1 for In the embodiment, L 1 for .

[0295] In the embodiment, HLEM is , , , or In this embodiment, HLEM is... In this embodiment, HLEM is... In this embodiment, HLEM is... In this embodiment, HLEM is... In this embodiment, HLEM is... .

[0296] In some embodiments, the compound comprises one to five optionally different half-life-extending motifs. In some embodiments, the compound comprises one to four optionally different half-life-extending motifs. In some embodiments, the compound comprises one to three optionally different half-life-extending motifs. In some embodiments, the compound comprises one to two optionally different half-life-extending motifs. In some embodiments, the compound comprises two to five different half-life-extending motifs. In some embodiments, the compound comprises two to four different half-life-extending motifs. In some embodiments, the compound comprises two to three different half-life-extending motifs. In some embodiments, the compound comprises two different half-life-extending motifs. In some embodiments, the compound comprises only one half-life-extending motif.

[0297] In an embodiment, the uptake motif independently has the following structure: (IV).

[0298] L 3 and L 4 Independently for the bond, -N(R) 23 )-, -O-, -S-, -C(O)-, -N(R 23 )C(O)-、-C(O)N(R 24 )-、-N(R 23 )C(O)N(R 24 -, -C(O)O-, -OC(O)-, -N(R) 23 )C(O)O-、-OC(O)N(R 24 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25 )-O-、-OP(S)(R 25 )-O-、-OP(O)(NR 23 R 24 -N-、-OP(S)(NR) 23 R 24 )-N-、-OP(O)(NR 23 R 24 )-O-、-OP(S)(NR 23 R 24 )-O-、-P(O)(NR 23 R 24 -N-、-P(S)(NR) 23 R 24 -N-、-P(O)(NR) 23 R 24 )-O-、-P(S)(NR 23 R 24 -O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. Each R 23 R 24 and R 25 Independently hydrogen or unsubstituted C1-C 10 alkyl.

[0299] L 5 -L 5A -L 5B -L 5C -L 5D -L 5E - and L 6 -L 6A -L 6B -L 6C -L 6D -L6E -. L 5A L 5B L 5C L 5D L 5E L 6A L 6B L 6C L 6D and L 6E Independently, it is a bond, -NH-, -O-, -S-, -C(O)-, -NHC(O)-, -NHC(O)NH-, -C(O)O-, -OC(O)-, -C(O)NH-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

[0300] R 1 and R 2 Independent for unsubstituted C1-C 25 Alkyl, wherein R 1 and R 2 At least one of them is unsubstituted C9-C 19 Alkyl group. In the examples, R 1 and R 2 Independent for unsubstituted C1-C 20 Alkyl, wherein R 1 and R 2 At least one of them is unsubstituted C9-C 19 alkyl.

[0301] R 3 It can be hydrogen, -NH2, -OH, -SH, -C(O)H, -C(O)NH2, -NHC(O)H, -NHC(O)OH, -NHC(O)NH2, -C(O)OH, -OC(O)H, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

[0302] t is an integer from 1 to 5.

[0303] In this embodiment, t is 1. In this embodiment, t is 2. In this embodiment, t is 3. In this embodiment, t is 4. In this embodiment, t is 5.

[0304] In the embodiment, an L 3 Linked to the 3' carbon of the oligonucleotide. In an example, an L... 3It is linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In an example, an L 3 Linked to the 5' carbon of the oligonucleotide. In an example, an L... 3 It is linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). In an example, an L 3 Linked to the 2' carbon of the oligonucleotide. In an example, an L... 3 Linked to the nucleobases of oligonucleotides.

[0305] In the embodiment, an L 3 It is linked to the 3' carbon of the oligonucleotide at the 3' end. In the example, an L 3 It is linked at the 3' end to the 3' nitrogen of an oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In an example, an L 3 It is linked to the 5' carbon of the oligonucleotide at the 5' end. In the example, an L 3 It is attached at the 5' end to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group).

[0306] In the embodiment, an L 3 The 3' end of the double-stranded oligonucleotide is attached to the 3' carbon of the double-stranded oligonucleotide. In an embodiment, an L 3 The 3' end of the antisense strand of the double-stranded oligonucleotide is linked to the 3' carbon of the double-stranded oligonucleotide. In an embodiment, an L 3 The 3' end of the sense strand of the double-stranded oligonucleotide is attached to the 3' carbon of the double-stranded oligonucleotide.

[0307] In the embodiment, an L 3 The 3' end of the double-stranded oligonucleotide is linked to a 3' nitrogen atom (e.g., the 3' nitrogen atom of the morpholino group). In an example, an L 3 The 3' end of the antisense strand of the double-stranded oligonucleotide is linked to the 3' nitrogen of the double-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In an example, an L 3 The 3' end of the sense strand of the double-stranded oligonucleotide is linked to the 3' nitrogen of the double-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group).

[0308] In the embodiment, an L 3 The 5' end of the double-stranded oligonucleotide is attached to the 5' carbon of the double-stranded oligonucleotide. In an embodiment, an L 3 The 5' end of the antisense strand of the double-stranded oligonucleotide is linked to the 5' carbon of the double-stranded oligonucleotide. In an embodiment, an L 3The sense strand of the double-stranded oligonucleotide is attached to the 5' carbon at the 5' end of the sense strand.

[0309] In the embodiment, an L 3 The 5' end of the double-stranded oligonucleotide is linked to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group). In an example, an L 3 The antisense strand of the double-stranded oligonucleotide is linked to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group). In an embodiment, an L 3 The sense strand of the double-stranded oligonucleotide is attached to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group) at the 5' end.

[0310] In the embodiment, an L 3 Linked to the 2' carbon of a double-stranded oligonucleotide. In an example, an L... 3 The 2' carbon of the double-stranded oligonucleotide is attached to either of its 3' ends. In an example, an L 3 The antisense strand of the double-stranded oligonucleotide is linked to the 2' carbon at the 3' end. In an embodiment, an L 3 The 2' carbon of the double-stranded oligonucleotide is attached to the 3' end of the sense strand. In an embodiment, an L 3 The 2' carbon of the double-stranded oligonucleotide is attached to either of its 5' ends. In an example, an L... 3 The antisense strand of the double-stranded oligonucleotide is linked to the 2' carbon at the 5' end. In an embodiment, an L 3 The sense strand of the double-stranded oligonucleotide is linked to the 2' carbon at the 5' end of the sense strand.

[0311] In the embodiment, an L 3 Linked to the nucleobases of a double-stranded oligonucleotide. In an example, an L... 3 The nucleobase of the double-stranded oligonucleotide is linked at either 3' end. In the example, an L... 3 The nucleobase of the double-stranded oligonucleotide is linked at the 3' end of the antisense strand. In the example, an L 3 The nucleobase of the double-stranded oligonucleotide is linked to the sense strand at the 3' end. In the example, an L... 3 The nucleobase of the double-stranded oligonucleotide is linked at either 5' end. In the example, an L... 3 The nucleobase of the double-stranded oligonucleotide is linked at the 5' end of the antisense strand. In the example, an L 3The sense strand of the double-stranded oligonucleotide is linked to a nucleobase at the 5' end of the sense strand.

[0312] In the embodiment, an L 3 It is linked to the 3' carbon of a single-stranded oligonucleotide at the 3' end. In the example, an L 3 The 3' end of the single-stranded oligonucleotide is linked to the 3' nitrogen of the single-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group).

[0313] In the embodiment, an L 3 It is linked to the 5' carbon of a single-stranded oligonucleotide at the 5' end.

[0314] In the embodiment, an L 3 It is attached at the 5' end to the 6' carbon of a single-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group).

[0315] In the embodiment, an L 3 Linked to the 2' carbon of a single-stranded oligonucleotide. In an example, an L... 3 It is linked to the 2' carbon of a single-stranded oligonucleotide at the 5' end. In the example, an L 3 It is linked to the 2' carbon of a single-stranded oligonucleotide at the 3' end.

[0316] In the embodiment, an L 3 Linked to the nucleobases of a single-stranded oligonucleotide. In an example, an L... 3 It is linked to the nucleobase of a single-stranded oligonucleotide at the 3' end. In the example, an L 3 It is linked to the nucleobase of a single-stranded oligonucleotide at the 5' end.

[0317] In the embodiment, L 3 For key, -N(R) 23 )-, -O-, -S-, -C(O)-, -N(R 23 )C(O)-、-C(O)N(R 24 )-、-N(R 23 )C(O)N(R 24 -, -C(O)O-, -OC(O)-, -N(R) 23 )C(O)O-、-OC(O)N(R 24 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25 )-O-、-OP(S)(R 25 )-O-、-OP(O)(NR 23 R 24 -N-、-OP(S)(NR) 23 R 24)-N-、-OP(O)(NR 23 R 24 )-O-、-OP(S)(NR 23 R 24 )-O-、-P(O)(NR 23 R 24 -N-、-P(S)(NR) 23 R 24 -N-、-P(O)(NR) 23 R 24 )-O-、-P(S)(NR 23 R 24 -O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene.

[0318] In the embodiment, L 3 As a key. In the embodiment, L 3 -N(R) 23 In the embodiment, L 3 It is either -O- or -S-. In the embodiment, L 3 It is -C(O)-. In the embodiment, L 3 -N(R) 23 C(O)- or -C(O)N(R) 24 In the embodiment, L 3 -N(R) 23 )C(O)N(R 24 In the embodiment, L 3 It is -C(O)O- or -OC(O)-. In the embodiment, L 3 -N(R) 23 )C(O)O-or-OC(O)N(R 24 In the embodiment, L 3 is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25 )-O-、-OP(O)(NR 23 R 24 )-N- or OP(O)(NR 23 R 24 )-O-. In the embodiment, L 3 -P(O)(NR) 23 R 24 -N-、-P(S)(NR) 23 R 24 -N-、-P(O)(NR)23 R 24 -O- or -P(S)(NR) 23 R 24 )-O-. In the embodiment, L 3 It is -SS-.

[0319] In the embodiment, L 3 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 23 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 3 Independently substituted alkylene groups (e.g., C1-C) 23 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 3 Independently unsubstituted alkylene (e.g., C1-C) 23 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 3 Independently substituted or unsubstituted C1-C 23 Alkylene. In the examples, L 3 Independently for substituted C1-C 23 Alkylene. In the examples, L 3 Independent for unsubstituted C1-C 23 Alkylene. In the examples, L 3 Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 3 Independently for substituted C1-C 12 Alkylene. In the examples, L 3 Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 3 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 3 Independently, it is a substituted C1-C8 alkylene group. In the examples, L 3 Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 3 Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 3 Independently, it is a substituted C1-C6 alkylene group. In the examples, L 3 Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 3Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 3 Independently, it is a substituted C1-C4 alkylene group. In the examples, L 3 Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 3 Independently, it is either substituted or unsubstituted ethylene. In the examples, L 3 Independently, it is a substituted ethylene. In the examples, L 3 Independently, it is an unsubstituted ethylene. In the examples, L 3 Independently, it is a substituted or unsubstituted methylene group. In the examples, L 3 Independently, it is a substituted methylene group. In the examples, L 3 Independently, it is an unsubstituted methylene group.

[0320] In the embodiment, L 3 Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 23 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 3 Independently, it is a substituted heteroalkylene group (e.g., 2 to 23 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 3 Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 23 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 3 Independently, it is a substituted or unsubstituted 2- to 23-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted 2- to 23-membered heteroalkylene group. In the examples, L 3 Independently, it is an unsubstituted 2- to 23-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 3 Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 3 Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted or unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 3Independently, it is a substituted 4- to 6-membered heteroalkylene group. In the examples, L 3 Independently, it is an unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted or unsubstituted 2- or 3-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted 2- to 3-membered heteroalkylene group. In the examples, L 3 Independently, it is an unsubstituted 2- to 3-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted or unsubstituted 4- to 5-membered heteroalkylene group. In the examples, L 3 Independently, it is a substituted 4- to 5-membered heteroalkylene group. In the examples, L 3 Independently, it is an unsubstituted 4- to 5-membered heteroalkylene group.

[0321] In the embodiment, L 4 For key, -N(R) 23 )-, -O-, -S-, -C(O)-, -N(R 23 )C(O)-、-C(O)N(R 24 )-、-N(R 23 )C(O)N(R 24 -, -C(O)O-, -OC(O)-, -N(R) 23 )C(O)O-、-OC(O)N(R 24 )-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25 )-O-、-OP(S)(R 25 )-O-、-OP(O)(NR 23 R 24 -N-、-OP(S)(NR) 23 R 24 )-N-、-OP(O)(NR 23 R 24 )-O-、-OP(S)(NR 23 R 24 )-O-、-P(O)(NR 23 R 24 -N-、-P(S)(NR) 23 R 24 -N-、-P(O)(NR) 23 R 24 )-O-、-P(S)(NR 23 R 24-O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene.

[0322] In the embodiment, L 4 As a key. In the embodiment, L 4 -N(R) 23 In the embodiment, L 4 It is either -O- or -S-. In the embodiment, L 4 It is -C(O)-. In the embodiment, L 4 -N(R) 23 C(O)- or -C(O)N(R) 24 In the embodiment, L 4 -N(R) 23 )C(O)N(R 24 In the embodiment, L 4 It is -C(O)O- or -OC(O)-. In the embodiment, L 4 -N(R) 23 )C(O)O-or-OC(O)N(R 24 In the embodiment, L 4 is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25 )-O-、-OP(O)(NR 23 R 24 )-N- or OP(O)(NR 23 R 24 )-O-. In the embodiment, L 4 -P(O)(NR) 23 R 24 -N-、-P(S)(NR) 23 R 24 -N-、-P(O)(NR) 23 R 24 -O- or -P(S)(NR) 23 R 24 )-O-. In the embodiment, L 4 It is -SS-.

[0323] In the embodiment, L 4 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 23 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 4Independently substituted alkylene groups (e.g., C1-C) 23 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 4 Independently unsubstituted alkylene (e.g., C1-C) 23 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 4 Independently substituted or unsubstituted C1-C 23 Alkylene. In the examples, L 4 Independently for substituted C1-C 23 Alkylene. In the examples, L 4 Independent for unsubstituted C1-C 23 Alkylene. In the examples, L 4 Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 4 Independently for substituted C1-C 12 Alkylene. In the examples, L 4 Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 4 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 4 Independently, it is a substituted C1-C8 alkylene group. In the examples, L 4 Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 4 Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 4 Independently, it is a substituted C1-C6 alkylene group. In the examples, L 4 Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 4 Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 4 Independently, it is a substituted C1-C4 alkylene group. In the examples, L 4 Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 4 Independently, it is either substituted or unsubstituted ethylene. In the examples, L 4 Independently, it is a substituted ethylene. In the examples, L 4 Independently, it is an unsubstituted ethylene. In the examples, L 4 Independently, it is a substituted or unsubstituted methylene group. In the examples, L 4Independently, it is a substituted methylene group. In the examples, L 4 Independently, it is an unsubstituted methylene group.

[0324] In the embodiment, L 4 Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 23 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 4 Independently, it is a substituted heteroalkylene group (e.g., 2 to 23 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 4 Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 23 quinone, 2 to 12 quinone, 2 to 8 quinone, 2 to 6 quinone, 4 to 6 quinone, 2 to 3 quinone, or 4 to 5 quinone). In the examples, L 4 Independently, it is a substituted or unsubstituted 2- to 23-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted 2- to 23-membered heteroalkylene group. In the examples, L 4 Independently, it is an unsubstituted 2- to 23-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 4 Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 4 Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted or unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted 4- to 6-membered heteroalkylene group. In the examples, L 4 Independently, it is an unsubstituted 4- to 6-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted or unsubstituted 2- or 3-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted 2- to 3-membered heteroalkylene group. In the examples, L 4 Independently, it is an unsubstituted 2- to 3-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted or unsubstituted 4- to 5-membered heteroalkylene group. In the examples, L 4 Independently, it is a substituted 4- to 5-membered heteroalkylene group. In the examples, L 4Independently, it is an unsubstituted 4- to 5-membered heteroalkylene group.

[0325] R 23 Independently hydrogen or unsubstituted alkyl (e.g., C1-C) 23 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, R 23 Independently hydrogen. In the examples, R 23 Independent for unsubstituted C1-C 23 Alkyl group. In the examples, R 23 Independently hydrogen or unsubstituted C1-C 12 Alkyl group. In the examples, R 23 Independently hydrogen or unsubstituted C1-C 10 Alkyl group. In the examples, R 23 Independently hydrogen or unsubstituted C1-C8 alkyl. In the examples, R 23 Independently hydrogen or unsubstituted C1-C6 alkyl. In the examples, R 23 Independently hydrogen or unsubstituted C1-C4 alkyl. In the examples, R 23 It is independently hydrogen or an unsubstituted C1-C2 alkyl group.

[0326] R 24 Independently hydrogen or unsubstituted alkyl (e.g., C1-C) 24 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, R 24 Independently hydrogen. In the examples, R 24 Independent for unsubstituted C1-C 24 Alkyl group. In the examples, R 24 Independently hydrogen or unsubstituted C1-C 12 Alkyl group. In the examples, R 24 Independently hydrogen or unsubstituted C1-C 10 Alkyl group. In the examples, R 24 Independently hydrogen or unsubstituted C1-C8 alkyl. In the examples, R 24 Independently hydrogen or unsubstituted C1-C6 alkyl. In the examples, R 24 Independently hydrogen or unsubstituted C1-C4 alkyl. In the examples, R 24 It is independently hydrogen or an unsubstituted C1-C2 alkyl group.

[0327] R 25 Independently hydrogen or unsubstituted alkyl (e.g., C1-C) 25 C1-C12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, R 25 Independently hydrogen. In the examples, R 25 Independent for unsubstituted C1-C 25 Alkyl group. In the examples, R 25 Independently hydrogen or unsubstituted C1-C 12 Alkyl group. In the examples, R 25 Independently hydrogen or unsubstituted C1-C 10 Alkyl group. In the examples, R 25 Independently hydrogen or unsubstituted C1-C8 alkyl. In the examples, R 25 Independently hydrogen or unsubstituted C1-C6 alkyl. In the examples, R 25 Independently hydrogen or unsubstituted C1-C4 alkyl. In the examples, R 25 It is independently hydrogen or an unsubstituted C1-C2 alkyl group.

[0328] In the embodiment, L 3 and L 4 Independently, it is a bond, -NH-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(CH3)-O-, -OP(S)(CH3)-O-, -OP(O)(N(CH3)2)-N-, -OP(O)(N(CH3)2)-O-, -OP(S)(N(CH3)2)-N-, -OP(S)(N(CH3)2)-O-, -P(O)(N(CH3)2)-N-, -P(O)(N(CH3)2)-O-, -P(S)(N(CH3)2)-N-, -P(S)(N(CH3)2)-O-, substituted or unsubstituted alkylene or substituted or unsubstituted heteroalkylene. In the examples, L 3Independently, it is a bond, -NH-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(CH3)-O-, -OP(S)(CH3)-O-, -OP(O)(N(CH3)2)-N-, -OP(O)(N(CH3)2)-O-, -OP(S)(N(CH3)2)-N-, -OP(S)(N(CH3)2)-O-, -P(O)(N(CH3)2)-N-, -P(O)(N(CH3)2)-O-, -P(S)(N(CH3)2)-N-, -P(S)(N(CH3)2)-O-, substituted or unsubstituted alkylene or substituted or unsubstituted heteroalkylene. In the examples, L 4 Independently, it is a bond, -NH-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(CH3)-O-, -OP(S)(CH3)-O-, -OP(O)(N(CH3)2)-N-, -OP(O)(N(CH3)2)-O-, -OP(S)(N(CH3)2)-N-, -OP(S)(N(CH3)2)-O-, -P(O)(N(CH3)2)-N-, -P(O)(N(CH3)2)-O-, -P(S)(N(CH3)2)-N-, -P(S)(N(CH3)2)-O-, substituted or unsubstituted alkylene or substituted or unsubstituted heteroalkylene.

[0329] In the embodiment, L 3 Independently In the embodiment, L 3 Independently -OPO2-O-. In the embodiment, L 3 Independently -OP(O)(S)-O-. In the embodiment, L 3 Independently -O-. In the embodiment, L 3 It is independently hydrogen-S-.

[0330] In the embodiment, L 3 It is linked to the 3' nitrogen of the morpholino group. In the examples, L 3 Independently -C(O)-. In the embodiment, L 3 It is linked to the 6' carbon of the morpholino group. In the examples, L 3 Independently, it is -OP(O)(N(CH3)2)-N-. In the embodiment, L 3 Independently -OP(O)(N(CH3)2)-O-. In the embodiment, L 3Independently -P(O)(N(CH3)2)-N-. In the embodiment, L 3 Independently, it is -P(O)(N(CH3)2)-O-.

[0331] In the embodiment, L 4 Independently, it is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-. In the embodiment, L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 7 Independently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 7 Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 , C1-C8, C1-C6, C1-C4 or C1-C2).

[0332] In the embodiment, L 4 Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 20 quinones, 2 to 12 quinones, 2 to 10 quinones, 2 to 8 quinones, 2 to 6 quinones, or 2 to 4 quinones). In the examples, L 4 Independently, it is a substituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 10 quinone, 2 to 8 quinone, 2 to 6 quinone, or 2 to 4 quinone). In the examples, L 4 Independently, it is an oxygen-substituted heteroalkylene group (e.g., 2 to 20 nucleotides, 2 to 12 nucleotides, 2 to 10 nucleotides, 2 to 8 nucleotides, 2 to 6 nucleotides, or 2 to 4 nucleotides). In the examples, L 4 Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 20, 2 to 12, 2 to 10, 2 to 8, 2 to 6, or 2 to 4).

[0333] In the embodiment, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12(C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 4 Independently for -L 7 -NH-C(O)-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 4 Independently for -L 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 , C1-C8, C1-C6, C1-C4 or C1-C2).

[0334] In the embodiment, L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 7 Independently substituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 7 Independently unsubstituted alkylene (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 7 Independently substituted or unsubstituted C1-C 20 Alkylene. In the examples, L 7 Independently for substituted C1-C 20 Alkylene. In the examples, L 7 Independently, it is a C1-C substituted with a hydroxyl group (OH). 20 Alkylene. In the examples, L 7 Independently, it is a C1-C substituted with hydroxymethyl. 20 Alkylene. In the examples, L 7 Independent for unsubstituted C1-C 20 Alkylene. In the examples, L 7 Independently substituted or unsubstituted C1-C 12 Alkylene. In the examples, L 7 Independently for substituted C1-C 12Alkylene. In the examples, L 7 Independently, it is a C1-C substituted with a hydroxyl group (OH). 12 Alkylene. In the examples, L 7 Independently, it is a C1-C substituted with hydroxymethyl. 12 Alkylene. In the examples, L 7 Independent for unsubstituted C1-C 12 Alkylene. In the examples, L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L 7 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, L 7 Independently, it is an unsubstituted C1-C8 alkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted C1-C6 alkylene group. In the examples, L 7 Independently, it is a substituted C1-C6 alkylene group. In the examples, L 7 Independently, it is a C1-C6 alkylene group substituted with a hydroxyl group (OH). In the examples, L 7 Independently, it is a C1-C6 alkylene group substituted with hydroxymethyl. In the examples, L 7 Independently, it is an unsubstituted C1-C6 alkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted C1-C4 alkylene group. In the examples, L 7 Independently, it is a substituted C1-C4 alkylene group. In the examples, L 7 Independently, it is a C1-C4 alkylene group substituted with a hydroxyl group (OH). In the examples, L 7 Independently, it is a C1-C4 alkylene group substituted with hydroxymethyl. In the examples, L 7 Independently, it is an unsubstituted C1-C4 alkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted C1-C2 alkylene group. In the examples, L 7 Independently, it is a substituted C1-C2 alkylene group. In the examples, L 7 Independently, it is a C1-C2 alkylene group substituted with a hydroxyl group (OH). In the examples, L 7 Independently, it is a C1-C2 alkylene group substituted with hydroxymethyl. In the examples, L 7 It is independently an unsubstituted C1-C2 alkylene group.

[0335] In the embodiment, L4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C1-C8 alkylene group.

[0336] In the embodiment, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted C3-C8 alkylene group. In the examples, L 4 Independently for -L 7-NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a C3-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a C3-C8 alkylene group substituted with hydroxymethyl. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C3-C8 alkylene group.

[0337] In the embodiment, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted C5-C8 alkylene group. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C5-C8 alkylene group.

[0338] In the embodiment, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7Independently, it is either substituted or unsubstituted octene. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted octene. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is octene substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is unsubstituted octene. In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is octene substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is octene substituted with hydroxymethyl. In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 It is an unsubstituted octene.

[0339] In the embodiment, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is either substituted or unsubstituted heptyl. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted heptyl group. In the embodiments, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a heptyl group substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7Independently, it is an unsubstituted heptyl group. In the embodiments, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is a heptyl group substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is a heptyl group substituted with hydroxymethyl. In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is an unsubstituted heptyl group.

[0340] In the embodiment, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is either substituted or unsubstituted hexylene. In the embodiments, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted hexylene. In the embodiments, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a hexanediol substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is unsubstituted hexylene. In the embodiment, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is a hexanediol substituted with a hydroxyl group (OH). In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is a hexanediol substituted with hydroxymethyl. In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is unreplaced ahejiki.

[0341] In the embodiment, L 4 Independently for -L7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is either substituted or unsubstituted pentylene. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a substituted pentylene. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is a hydroxyl (OH)-substituted pentylene. In the examples, L 4 Independently for -L 7 -NH-C(O)- or -L 7 -C(O)-NH-; and L 7 Independently, it is an unsubstituted pentylene. In the embodiments, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is a hydroxyl (OH)-substituted pentylene. In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is a hydroxymethyl-substituted pentylene. In the examples, L 4 Independently for -L 7 -NH-C(O)-, and L 7 Independently, it is an unsubstituted pentylene.

[0342] In the embodiment, L 4 Independently In the embodiment, L 4 Independently In the embodiment, L 4 Independently In the embodiment, L 4 Independently In the embodiment, L 4 Independently In the embodiment, L 4 Independently .

[0343] In the embodiment, L 4 Independently In the embodiment, L 4 Independently In the embodiment, L4 Independently In the embodiment, L 4 Independently In the embodiment, L 4 Independently In the embodiment, L 4 Independently .

[0344] In the embodiment, -L 3 -L 4 -Independently for-L 7 -NH-C(O)- or -L 7 -C(O)-NH-. In the embodiment, L 7 Independently, it is a substituted or unsubstituted heteroalkylene group (e.g., 2 to 20 quinones, 2 to 12 quinones, 2 to 10 quinones, 2 to 8 quinones, 2 to 6 quinones, or 2 to 4 quinones). In the examples, L 7 Independently, it is a substituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 10 quinone, 2 to 8 quinone, 2 to 6 quinone, or 2 to 4 quinone). In the examples, L 7 Independently, it is an oxygen-substituted heteroalkylene group (e.g., 2 to 20 nucleotides, 2 to 12 nucleotides, 2 to 10 nucleotides, 2 to 8 nucleotides, 2 to 6 nucleotides, or 2 to 4 nucleotides). In the examples, L 7 Independently, it is an unsubstituted heteroalkylene group (e.g., 2 to 20 quinone, 2 to 12 quinone, 2 to 10 quinone, 2 to 8 quinone, 2 to 6 quinone, or 2 to 4 quinone). In the examples, L 7 Independently, it is a substituted or unsubstituted hemienyl group (e.g., 2 to 20 quinones, 2 to 12 quinones, 2 to 10 quinones, 2 to 8 quinones, 2 to 6 quinones, or 2 to 4 quinones). In the examples, L 7 Independently, it is a substituted hemienyl group (e.g., 2 to 20 ternary, 2 to 12 ternary, 2 to 10 ternary, 2 to 8 ternary, 2 to 6 ternary, or 2 to 4 ternary). In the examples, L 7 Independently, it is an oxygen-substituted hesene group (e.g., 2 to 20 ternary, 2 to 12 ternary, 2 to 10 ternary, 2 to 8 ternary, 2 to 6 ternary, or 2 to 4 ternary). In the examples, L 7 Independently unsubstituted hemienyl groups (e.g., 2 to 20, 2 to 12, 2 to 10, 2 to 8, 2 to 6, or 2 to 4).

[0345] In the embodiment, L 7 Independently, it is a substituted or unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted 2- to 20-membered heteroalkylene group. In the examples, L 7 Independently, it is a 2- to 20-membered heteroalkylene group substituted with an oxygen. In the examples, L7 Independently, it is an unsubstituted 2- to 20-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 12-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted 2- to 12-membered heteroalkylene group. In the examples, L 7 Independently, it is a 2- to 12-membered heteroalkylene group substituted with an oxygen. In the examples, L 7 Independently, it is an unsubstituted 2- to 12-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted 2- to 10-membered heteroalkylene group. In the examples, L 7 Independently, it is a 2- to 10-membered heteroalkylene group substituted with an oxygen group. In the examples, L 7 Independently, it is an unsubstituted 2- to 10-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted 2- to 8-membered heteroalkylene group. In the examples, L 7 Independently, it is a 2- to 8-membered heteroalkylene group substituted with an oxygen. In the examples, L 7 Independently, it is an unsubstituted 2- to 8-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted 2- to 6-membered heteroalkylene group. In the examples, L 7 Independently, it is a 2- to 6-membered heteroalkylene group substituted with an oxygen. In the examples, L 7 Independently, it is an unsubstituted 2- to 6-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 4-membered heteroalkylene group. In the examples, L 7 Independently, it is a substituted 2- to 4-membered heteroalkylene group. In the examples, L 7 Independently, it is a 2- to 4-membered heteroalkylene group substituted with an oxygen. In the examples, L 7 Independently, it is an unsubstituted 2 to 4-membered heteroalkylene group.

[0346] In the embodiment, L 7 Independently, it is a substituted or unsubstituted 2- to 20-membered hemienyl group. In the examples, L 7 Independently, it is a substituted 2- to 20-membered hemienyl group. In the examples, L 7 Independently, it is a 2- to 20-membered heterene group substituted with an oxygen group. In the examples, L 7Independently, it is an unsubstituted 2- to 20-membered hemienyl group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 12-membered hemienyl group. In the examples, L 7 Independently, it is a substituted 2- to 12-membered hemienyl group. In the examples, L 7 Independently, it is a 2- to 12-membered heteroene group substituted with an oxygen group. In the examples, L 7 Independently, it is an unsubstituted 2- to 12-membered hemienyl group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 10-membered hemienyl group. In the examples, L 7 Independently, it is a substituted 2- to 10-membered hemienyl group. In the examples, L 7 Independently, it is a 2- to 10-membered heterene group substituted with an oxygen group. In the examples, L 7 Independently, it is an unsubstituted 2- to 10-membered hemienyl group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 8-membered heterene group. In the examples, L 7 Independently, it is a substituted 2- to 8-membered hemienyl group. In the examples, L 7 Independently, it is a 2- to 8-membered heterene group substituted with an oxygen group. In the examples, L 7 Independently, it is an unsubstituted 2- to 8-membered hemienyl group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 6-membered hemienyl group. In the examples, L 7 Independently, it is a substituted 2- to 6-membered hemienyl group. In the examples, L 7 Independently, it is a 2- to 6-membered heterene group substituted with an oxygen group. In the examples, L 7 Independently, it is an unsubstituted 2- to 6-membered hemienyl group. In the examples, L 7 Independently, it is a substituted or unsubstituted 2- to 4-membered heterene group. In the examples, L 7 Independently, it is a substituted 2- to 4-membered hemienyl group. In the examples, L 7 Independently, it is a 2- to 4-membered hemienyl group substituted with an oxygen group. In the examples, L 7 Independently, it is an unsubstituted 2 to 4-membered heteroene group.

[0347] In the embodiment, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)- or -OL 7 -C(O)-NH-. In the embodiment, L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)- or -OL 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 , C1-C8, C1-C6, C1-C4 or C1-C2).

[0348] In the embodiment, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-, and L 7Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C1-C8 alkylene group.

[0349] In the embodiment, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a C3-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-, and L 7 Independently, it is a C3-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C3-C8 alkylene group.

[0350] In the embodiment, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-, and L 7 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C5-C8 alkylene group.

[0351] In the embodiment, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C1-C8 alkylene group.

[0352] In the embodiment, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7Independently, it is a substituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a C3-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a C3-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C3-C8 alkylene group.

[0353] In the embodiment, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C5-C8 alkylene group.

[0354] In the embodiment, -L 3 -L 4 - Independently for , or In the embodiment, -L3 -L 4 - Independently for In the embodiment, -L 3 -L 4 - Independently for In the embodiment, -L 3 -L 4 - Independently for .

[0355] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-、-OP(O)(S)-OL 7 -NH-C(O)-、-OPO2-OL 7 -C(O)-NH- or -OP(O)(S)-OL 7 -C(O)-NH-. In the embodiment, L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)- or -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH- or -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted alkylene group. In the examples, -L 3 -L 4-Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 It is independently a substituted or unsubstituted alkylene group.

[0356] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)- or -OPO2-OL 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 , C1-C8, C1-C6, C1-C4 or C1-C2).

[0357] In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)- or -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 (C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently substituted or unsubstituted alkylene groups (e.g., C1-C) 20 C1-C 12 , C1-C8, C1-C6, C1-C4 or C1-C2).

[0358] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C1-C8 alkylene group.

[0359] In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C1-C8 alkylene group.

[0360] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a C3-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a C3-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C3-C8 alkylene group.

[0361] In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a C3-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a C3-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C3-C8 alkylene group.

[0362] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L7 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C5-C8 alkylene group.

[0363] In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a substituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -C(O)-NH-; and L 7 It is independently an unsubstituted C5-C8 alkylene group.

[0364] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, -L 3 -L4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C1-C8 alkylene group.

[0365] In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C1-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)2-OL 7 -NH-C(O)-; and L 7 Independently, it is a C1-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a C1-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C1-C8 alkylene group.

[0366] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a C3-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a C3-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C3-C8 alkylene group.

[0367] In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C3-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a C3-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7-NH-C(O)-; and L 7 Independently, it is a C3-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C3-C8 alkylene group.

[0368] In the embodiment, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for-OPO2-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C5-C8 alkylene group.

[0369] In the embodiment, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted or unsubstituted C5-C8 alkylene group. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a substituted C5-C8 alkylene group. In the examples, -L 3-L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a C5-C8 alkylene group substituted with a hydroxyl group (OH). In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 Independently, it is a C5-C8 alkylene group substituted with hydroxymethyl. In the examples, -L 3 -L 4 -Independently for -OP(O)(S)-OL 7 -NH-C(O)-; and L 7 It is independently an unsubstituted C5-C8 alkylene group.

[0370] In the embodiment, -L 3 -L 4 - Linked to the 3' carbon of the oligonucleotide. In the examples, -L 3 -L 4 - Linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the examples, -L 3 -L 4 - Linked to the 5' carbon of the oligonucleotide. In the examples, -L 3 -L 4 - Linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). In the examples, -L 3 -L 4 - Linked to the 2' carbon of the oligonucleotide. In the examples, -L 3 -L 4 - Linked to the nucleobases of oligonucleotides.

[0371] In the embodiment, at least -L 3 -L 4 - It is linked to the 3' carbon of the oligonucleotide at the 3' end. In the examples, at least -L 3 -L 4 - It is linked at the 3' end to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the examples, at least -L 3 -L 4 - It is linked to the 5' carbon of the oligonucleotide at the 5' end. In the examples, at least -L 3 -L 4 - It is attached to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group) at the 5' end.

[0372] In the embodiment, -L 3 -L4 - Independently for , , , , , , , , , , or .

[0373] In the embodiment, -L 3 -L 4 - Independently for , or , In the embodiment, -L 3 -L 4 - Independently for or In the embodiment, -L 3 -L 4 - Independently for or In the embodiment, -L 3 -L 4 - Independently for or In the embodiment, -L 3 -L 4 - Independently for or .

[0374] In the embodiment, -L 3 -L 4 - Independently for , , or It is also linked to the 3' carbon of the oligonucleotide.

[0375] In the embodiment, -L 3 -L 4 - Independently linked to the 3' carbon of the oligonucleotide or In the embodiment, -L 3 -L 4 - Independently linked to the 3' carbon of the oligonucleotide or .

[0376] In the embodiment, -L 3 -L 4 - Independently for or And it is linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the examples, -L 3 -L 4 - Independently linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the embodiment, -L 3 -L 4 - Independently linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). .

[0377] In the embodiment, -L 3 -L 4 - Independently for , , or And it is linked to the 5' carbon of the oligonucleotide. In the examples, -L 3 -L 4 - Independently linked to the 5' carbon of the oligonucleotide or In the embodiment, -L 3 -L 4 - Independently linked to the 5' carbon of the oligonucleotide or .

[0378] In embodiments where the oligonucleotide includes a morpholino group, L 3 Independently, it is -P(O)(N(CH3)2)-N- or -P(O)(N(CH3)2)-O-. In the embodiments, L 4 It is a substituted or unsubstituted heterocyclic alkyl group. In the examples, L 4 It is a substituted heterocyclic alkyl group. In the examples, L 4 It is an unsubstituted heterocyclic alkyl group. In the examples, L 4 It is a substituted or unsubstituted piperidinyl group. In the examples, L 4 It is a substituted piperidinyl group. In the examples, L 4 It is an unsubstituted piperidinyl group. In the examples, L 4 It is a substituted or unsubstituted piperazine group. In the examples, L 4 It is a substituted piperazine group. In the examples, L 4 It is an unsubstituted piperazine group. In the examples, -L 3 -L 4 - Independently linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). or In the embodiment, -L 3 -L4 - Independently linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). In the embodiment, -L 3 -L 4 - Independently linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). .

[0379] In the embodiment, -L 3 -L 4 - Independently linked to the nucleobases of the oligonucleotide. In the examples, -L 3 -L 4 - Independently for And it is linked to the nucleobases of oligonucleotides.

[0380] In the embodiment, -L 3 -L 4 - Linked to the 3' carbon of the double-stranded oligonucleotide at either 3' end. In the examples, -L 3 -L 4 - It is attached to the 3' carbon of the double-stranded oligonucleotide at the 3' end of the antisense strand. In the embodiment, -L 3 -L 4 - The 3' end of the sense strand of the double-stranded oligonucleotide is attached to the 3' carbon of the double-stranded oligonucleotide.

[0381] In the embodiment, -L 3 -L 4 - Linked to the 3' nitrogen of the double-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group) at either 3' end. In the examples, -L 3 -L 4 - The 3' end of the antisense strand of the double-stranded oligonucleotide is linked to the 3' nitrogen of the double-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the examples, -L 3 -L 4 - The 3' nitrogen of the double-stranded oligonucleotide (e.g., PMO) is attached to the 3' end of the sense strand.

[0382] In the embodiment, -L 3 -L 4 - Linked to the 5' carbon of the double-stranded oligonucleotide at either 5' end. In the examples, -L 3 -L 4 - It is attached to the 5' end of the antisense strand of the double-stranded oligonucleotide at the 5' carbon. In the embodiment, -L 3 -L 4- The 5' end of the sense strand of the double-stranded oligonucleotide is attached to the 5' carbon of the double-stranded oligonucleotide.

[0383] In the embodiment, -L 3 -L 4 - Linked to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group) at either of the 5' ends. In the examples, -L 3 -L 4 - The antisense strand of the double-stranded oligonucleotide is linked to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group) at the 5' end. In the examples, -L 3 -L 4 - The 5' end of the sense strand of the double-stranded oligonucleotide is attached to the 6' carbon of the double-stranded oligonucleotide (e.g., the 6' carbon of the morpholino group).

[0384] In the embodiment, -L 3 -L 4 - Linked to the 2' carbon of the double-stranded oligonucleotide. In the examples, -L 3 -L 4 - Linked to the 2' carbon of the double-stranded oligonucleotide at either 3' end. In the examples, -L 3 -L 4 - It is linked to the 2' carbon of the double-stranded oligonucleotide at the 3' end of the antisense strand. In the embodiment, -L 3 -L 4 - It is linked to the 2' carbon of the double-stranded oligonucleotide at the 3' end of the sense strand. In the embodiment, -L 3 -L 4 - Linked to the 2' carbon of the double-stranded oligonucleotide at either 5' end. In the examples, -L 3 -L 4 - It is linked to the 2' carbon of the double-stranded oligonucleotide at the 5' end of the antisense strand. In the example, -L 3 -L 4 - The sense strand of the double-stranded oligonucleotide is attached to the 2' carbon at the 5' end of the sense strand.

[0385] In the embodiment, -L 3 -L 4 - Linked to the nucleobases of the double-stranded oligonucleotide. In the examples, -L 3 -L 4 - Linked to a nucleobase of the double-stranded oligonucleotide at either 3' end. In an example, -L 3 -L 4- The nucleobase of the double-stranded oligonucleotide is linked at the 3' end of the antisense strand. In the example, -L 3 -L 4 - The nucleobase of the double-stranded oligonucleotide is linked at the 3' end of the sense strand. In the example, -L 3 -L 4 - Linked to a nucleobase of the double-stranded oligonucleotide at either 5' end. In an example, -L 3 -L 4 - The nucleobase of the double-stranded oligonucleotide is linked at the 5' end of the antisense strand. In the example, -L 3 -L 4 - The nucleobase of the double-stranded oligonucleotide is linked to the sense strand at the 5' end of the double-stranded oligonucleotide.

[0386] In the embodiment, -L 3 -L 4 - It is linked to the 3' carbon of a single-stranded oligonucleotide at the 3' end.

[0387] In the embodiment, -L 3 -L 4 - It is attached to the 3' nitrogen of a single-stranded oligonucleotide (e.g., the 3' nitrogen of the morpholino group) at the 3' end.

[0388] In the embodiment, -L 3 -L 4 - Linked to the 5' carbon of the single-stranded oligonucleotide at the 5' end.

[0389] In the embodiment, -L 3 -L 4 - It is linked at the 5' end of the single-stranded oligonucleotide to the 6' carbon (e.g., the 6' carbon of the morpholino group). In the examples, -L 3 -L 4 - Independently for .

[0390] In the embodiment, -L 3 -L 4 - Linked to the 2' carbon of a single-stranded oligonucleotide. In the examples, -L 3 -L 4 - It is linked to the 2' carbon of a single-stranded oligonucleotide at the 3' end. In the example, -L 3 -L 4 - It is linked to the 2' carbon of a single-stranded oligonucleotide at the 5' end.

[0391] In the embodiment, -L 3 -L 4- Linked to the nucleobases of a single-stranded oligonucleotide. In the examples, -L 3 -L 4 - It is linked to the nucleobase of the single-stranded oligonucleotide at the 3' end. In the example, -L 3 -L 4 - Linked to the nucleobase of the single-stranded oligonucleotide at the 5' end.

[0392] In the embodiment, -L 3 -L 4 - Independently for , , , , or .

[0393] In the embodiment, -L 3 -L 4 - Independently linked to the 3' carbon of the oligonucleotide or In the embodiment, -L 3 -L 4 - Independently linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). or In the embodiment, -L 3 -L 4 - Independently linked to the 5' carbon of the oligonucleotide or In the embodiment, -L 3 -L 4 - Independently linked to the 6' carbon of the oligonucleotide (e.g., the 6' carbon of the morpholino group). or In the embodiment, -L 3 -L 4 - Independently linked to the 2' carbon of the oligonucleotide or In the embodiment, -L 3 -L 4 - Independently linked to the nucleobases of oligonucleotides or .

[0394] In the embodiment, -L 3 -L 4 - Independently linked to the 3' carbon of the oligonucleotide or In the embodiment, -L3 -L 4 - Independently linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). or In the embodiment, -L 3 -L 4 - Independently linked to the 5' carbon of the oligonucleotide or In the embodiment, -L 3 -L 4 - Independently linked to the 6' carbon of an oligonucleotide (e.g., the 6' carbon of the morpholino group MO). or In the embodiment, -L 3 -L 4 - Independently linked to the 2' carbon of the oligonucleotide or In the embodiment, -L 3 -L 4 - Independently linked to the nucleobases of oligonucleotides or .

[0395] In the embodiment, -L 3 -L 4 - Independently linked to the 3' carbon of the oligonucleotide In the embodiment, -L 3 -L 4 - Independently linked to the 3' nitrogen of the oligonucleotide (e.g., the 3' nitrogen of the morpholino group). In the embodiment, -L 3 -L 4 - Independently for And it is linked to the 5' carbon of the oligonucleotide. In the examples, -L 3 -L 4 - Independently linked to the 6' carbon of the ol...

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, (HLEM) z -A(I), in: (A) is a single-stranded or double-stranded oligonucleotide covalently bonded to a half-life extension motif (HLEM). The double-stranded oligonucleotides mentioned above are small interfering RNAs, which contain: a) Antisense strand and sense strand, wherein the antisense strand and sense strand are 17 to 25 nucleotides in length; b) One or more modified nucleotides comprising a modified sugar moiety, said modified sugar moiety comprising a 2'-modification selected from: 2'- O -Methyl modification, 2'- O -Methoxyethyl modification, 2'-fluorine modification and 2'-deoxy-2'-fluorine modification; and c) One or more modified nucleotide bonds selected from: thiophosphate bonds, phosphoramide bonds, and phosphodiamid bonds; The single-stranded oligonucleotides mentioned above are small interfering RNAs, which contain: a) 15 to 25 nucleotides in length, b) One or more modified nucleotides comprising a modified sugar moiety, said modified sugar moiety comprising a 2'-modification selected from: 2'- O -Methyl modification, 2'- O -Methoxyethyl modification, 2'-fluorine modification and 2'-deoxy-2'-fluorine modification; and c) One or more modified nucleotide bonds selected from: thiophosphate bonds and phosphodiamid bonds; z is 1; The extended half-life motif is shown in equation (III): (III), in: k is 1; L 2 For unreplaced C2-C 22 Alkylene and a)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -;in: L 1A It can be -OPO2-O- or -OP(O)(S)-O-; L 1B -L 10 -NH-C(O)- or -L 10 -C(O)-NH-, where L 10 C1-C is a hydroxymethyl-substituted C1-C 20 Alkylene or unsubstituted C1-C 20 Alkylene; L 1C For key or R 1C - Replacement C1-C 10 Alkylene; L 1D For the bond, unsubstituted C1-C 20 Alkylene, or 5 to 8-membered heteroalkylene, either oxy-substituted or unsubstituted; L 1E For bonds, -NHC(O)- or -C(O)NH-; R 1C –NHC(O)-L 2C -R 8C ; L 2C For the bond or unsubstituted C2-C 22 Alkylene, and R 8C It can be hydrogen, C1-C3 alkyl, or –COOH; or b)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -;in: L 1A It is -OPO2-O- or -OP(O)(S)-O; L 1B C1-C is a hydroxymethyl-substituted C1-C 20 Alkylene, unsubstituted C1-C 20 Alkylene or unsubstituted 2 to 20-membered heteroalkylene; L 1C -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 21 - or -OPO2-O-; L 1D For the bond, unsubstituted C1-C 20 Alkylene or R 1D - Replacement C1-C 10 Alkylene; L 1E For bonds, -NHC(O)- or -C(O)NH-; R 1D Independently -NHC(O)-L 2D -R 8D ; L 2D For the bond or unsubstituted C2-C 22 Alkylene; R 8D It is hydrogen, C1-C3 alkyl, or –COOH, and Each R 20 R 21 and R 22 Hydrogen or unsubstituted C1-C 10 alkyl; or c)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -; in: L 1A -L 1B -for or ; L 1C For R 1C - Replacement C1-C 10 Alkylene; L 1D For the bond, unsubstituted C1-C 20 Alkylene, or 5 to 8-membered heteroalkylene, either oxy-substituted or unsubstituted; L 1E -N(R) 20 C(O)- or -C(O)N(R) 21 )-; Each R 20 and R 21 Hydrogen or unsubstituted C1-C 10 alkyl; R 1C -NHC(O)-L 2C -R 8C ; L 2C For key or unreplaced C 10 -C 22 Alkylene, and R 8C It can be hydrogen, C1-C3 alkyl, or -COOH; or d)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -;in: L 1A -L 1B -for or ,and -L 1C -L 1D -L 1E -for , or .

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L 1A It is -OPO2-O-.

3. The compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein L 1B For –L 10 -NH-C(O)- or –L 10 -C(O)-NH-, where L 10 It is a hydroxymethyl-substituted C1-C8 alkylene group or an unsubstituted C1-C8 alkylene group.

4. The compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein L 1B for or .

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein –L 1A -L 1B -for , , , or .

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein –L 1A -L 1B -for-OPO2-OL 10 -NH-C(O)-, where L 10 C1-C is a hydroxymethyl-substituted C1-C 12 Alkylene or unsubstituted C1-C 12 Alkylene.

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein... –L 1A -L 1B -for ,or And linked to the 3' carbon of the oligonucleotide; or or –L 1A -L 1B -for or And it is linked to the 5' carbon of the oligonucleotide.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L 1 for: , , , , , , , , , , , , , , , , , , , , , , or .

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the half-life-extending motif (HLEM) is ; ; ; ; ; ; ; ;or .

10. Compounds of formula (II) or pharmaceutically acceptable salts thereof: (HLEM) z -A-(UM) t (II), in: (A) consists of single-stranded or double-stranded oligonucleotides covalently bonded to a half-life extension motif (HLEM) and an uptake motif (UM). The double-stranded oligonucleotides mentioned above are small interfering RNAs, which contain: a) Antisense strand and sense strand, wherein the length of the antisense strand and sense strand is 17 to 25 nucleotides; b) One or more modified nucleotides comprising a modified sugar moiety, said modified sugar moiety comprising a 2'-modification selected from: 2'- O -Methyl modification, 2'- O -Methoxyethyl modification, 2'-fluorine modification and 2'-deoxy-2'-fluorine modification; and c) One or more modified nucleotide bonds selected from: thiophosphate bonds and phosphodiamid bonds; The single-stranded oligonucleotides mentioned above are single-stranded small interfering RNAs, which contain: d) 15 to 25 nucleotides in length, e) One or more modified nucleotides comprising a modified sugar moiety, said modified sugar moiety comprising a 2'-modification selected from: 2'- O -Methyl modification, 2'- O -Methoxyethyl modification, 2'-fluorine modification and 2'-deoxy-2'-fluorine modification; and f) One or more modified nucleotide bonds selected from: thiophosphate bonds, phosphoramide bonds, and phosphodiamid bonds; t is 1; z is 1; The half-life extended motif described therein has the structure of formula (III): (III) in: k is 1; L 2 For unreplaced C2-C 22 Alkylene and a)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -; in: L 1A It can be -OPO2-O- or -OP(O)(S)-O-; L 1B -L 10 -NH-C(O)- or -L 10 -C(O)-NH-, where L 10 C1-C is a hydroxymethyl-substituted C1-C 20 Alkylene or unsubstituted C1-C 20 Alkylene; L 1C For key or R 1C - Replacement C1-C 10 Alkylene; L 1D For the bond, unsubstituted C1-C 20 Alkylene, or 5 to 8-membered heteroalkylene, either oxy-substituted or unsubstituted; L 1E For bonds, -NHC(O)- or -C(O)NH-; R 1C Independently –NHC(O)-L 2C -R 8C ; L 2C For the bond or unsubstituted C2-C 22 Alkylene, and R 8C It can be hydrogen, C1-C3 alkyl, or –COOH; or b)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -; in: L 1A It is -OPO2-O- or -OP(O)(S)-O; L 1B C1-C is a hydroxymethyl-substituted C1-C 20 Alkylene, unsubstituted C1-C 20 Alkylene or unsubstituted 2 to 20-membered heteroalkylene; L 1C -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 21 - or -OPO2-O-; L 1D For the bond, unsubstituted C1-C 20 Alkylene or R 1D - Replacement C1-C 10 Alkylene; L 1E For bonds, -NHC(O)- or -C(O)NH-; R 1D Independently -NHC(O)-L 2D -R 8D ; L 2D For the bond or unsubstituted C2-C 22 Alkylene; R 8D It is hydrogen, C1-C3 alkyl, or –COOH, and Each R 20 R 21 and R 22 Hydrogen or unsubstituted C1-C 10 alkyl; or c)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -;in: L 1A -L 1B -for or ; L 1C For R 1C - Replacement C1-C 10 Alkylene; L 1D For the bond, unsubstituted C1-C 20 Alkylene, or 5 to 8-membered heteroalkylene, either oxy-substituted or unsubstituted; L 1E -N(R) 20 C(O)- or -C(O)N(R) 21 )-; Each R 20 and R 21 Hydrogen or unsubstituted C1-C 10 alkyl; R 1C -NHC(O)-L 2C -R 8C ; L 2C For key or unreplaced C 10 -C 22 Alkylene, and R 8C It can be hydrogen, C1-C3 alkyl, or -COOH; or d)L 1 -L 1A -L 1B -L 1C -L 1D -L 1E -;in: L 1A -L 1B -for or ,and -L 1C -L 1D -L 1E -for , or ； The uptake motif described therein has the structure of formula (IV): (IV), in: L 3 It can be -OPO2-O- or -OP(O)(S)-O-; L 4 For –L 7 -NH-C(O)- or –L 7 -C(O)-NH-, where L 7 C1-C is a hydroxymethyl-substituted C1-C 20 Alkylene or unsubstituted C1-C 20 Alkylene, or oxy-substituted 2 to 20-membered heteroalkylene or unsubstituted 2 to 20-membered heteroalkylene; L 5 -L 5A -L 5B -L 5C -L 5D -L 5E -,in: L 5A For bond or unsubstituted C1-C 20 Alkylene; L 5B It is a bonded or unsubstituted phenylene; L 5C For the bond, unsubstituted C1-C 20 Alkylene, unsubstituted C2-C 20 Alynyl or unsubstituted phenylene; L 5D For bond or unsubstituted C1-C 20 Alkylene; L 5E It is -NHC(O)-; L 6 It is -NHC(O)-; R 1 and R 2 For unreplaced C1-C 25 Alkyl, wherein R 1 and R 2 At least one of them is unsubstituted C9-C 19 Alkyl; and R 3 It is hydrogen.

11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein L 3 It is -OPO2-O-.

12. The compound of claim 10 or claim 11, or a pharmaceutically acceptable salt thereof, wherein L 4 -L 7 -NH-C(O)- or –L 7 -C(O)-NH-, where the hydroxymethyl-substituted C1-C 20 Alkylene or unsubstituted C1-C 20 Alkylene.

13. The compound according to any one of claims 10 to 12, or a pharmaceutically acceptable salt thereof, wherein L 4 for or .

14. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein –L 3 -L 4 -for-OPO2-OL 7 -NH-C(O)-, where L 7 It is a hydroxymethyl-substituted C5-C8 alkylene group or an unsubstituted C5-C8 alkylene group.

15. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein –L 3 -L 4 -for , or .

16. The compound according to any one of claims 10 to 15, or a pharmaceutically acceptable salt thereof, wherein L 5 -NHC(O)-, , , , or .

17. The compound according to any one of claims 10 to 16, or a pharmaceutically acceptable salt thereof, wherein L 5A It is a bonded or unsubstituted C1-C8 alkylene group; L 5B It is a bond, -NHC(O)- or an unsubstituted phenylene; L 5C It is a bond, an unsubstituted C2-C8 ynylene group or an unsubstituted phenylene group; L 5D It is a bonded or unsubstituted C1-C8 alkylene group; and L 5E It is -NHC(O)-.

18. The compound according to any one of claims 10 to 17, or a pharmaceutically acceptable salt thereof, wherein R 1 For unreplaced C1-C 17 alkyl.

19. The compound of claim 18 or a pharmaceutically acceptable salt thereof, wherein R 1 For unreplaced C 13 -C 17 alkyl.

20. The compound according to any one of claims 10 to 19, or a pharmaceutically acceptable salt thereof, wherein R 2 For unreplaced C 13 -C 17 alkyl.

21. The compound according to any one of claims 10 to 20, or a pharmaceutically acceptable salt thereof, wherein L 1A It is -OPO2-O-.

22. The compound of claim 10 or claim 20, or a pharmaceutically acceptable salt thereof, wherein L 1B For –L 10 -NH-C(O)- or –L 10 -C(O)-NH-, where L 10 It is a hydroxymethyl-substituted C1-C8 alkylene group or an unsubstituted C1-C8 alkylene group.

23. The compound of claim 10 or claim 20, or a pharmaceutically acceptable salt thereof, wherein L 1B for or .

24. The compound according to any one of claims 10 to 20, or a pharmaceutically acceptable salt thereof, wherein –L 1A -L 1B -for , , , or .

25. The compound according to any one of claims 10 to 20, or a pharmaceutically acceptable salt thereof, wherein –L 1A -L 1B -for-OPO2-OL 10 -NH-C(O)-, where L 10 C1-C is a hydroxymethyl-substituted C1-C 12 Alkylene or unsubstituted C1-C 12 Alkylene.

26. The compound according to any one of claims 10 to 20, or a pharmaceutically acceptable salt thereof, wherein –L 1A -L 1B -for or And linked to the 3' carbon of the oligonucleotide; or or –L 1A -L 1B -for or And it is linked to the 5' carbon of the oligonucleotide.

27. The compound according to any one of claims 10 to 20, or a pharmaceutically acceptable salt thereof, wherein L 1 for: , , , , , , , , , , , , , , , , , , , , , , or .

28. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the half-life-extending motif (HLEM) is ; ; ; ; ; ; ; ;or .

29. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-28.

Images