Nucleic acid and compounds containing half-life motifs

Abstract

This invention provides improved nucleic acid compounds and methods for introducing such compounds into cells. [Solution] A compound is provided that contains nucleic acid (A) covalently bonded to a half-life extension motif (HLEM).

Description

Technical Field

[0001] Cross - reference to related applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 940,83 filed on November 26, 2019, the entire disclosure of which is incorporated herein by reference for all purposes.

[0002] Reference to a "Sequence Listing", table, or computer program listing appendix document submitted as an ASCII file The listing described in the file DTX - 003 - 01WO_ST25.TXT (created on November 23, 2020 , size 1,174 bytes, machine format IBM - PC, MS Windows operating system) is incorporated herein by reference.

[0003] The present disclosure relates to the field of biologically active compounds containing nucleic acids. More specifically, the present disclosure relates to compounds containing nucleic acids, their preparation, and their use.

Background Art

[0004] Delivering therapeutic nucleic acids to cells remains a challenging area of research. Thus, there is a need for improved nucleic acid compounds and strategies for introducing such compounds into cells.

Summary of the Invention

[0005] Provided herein is, inter alia, a compound comprising a nucleic acid (A) covalently linked to a compound, or a half - life extension motif (HLEM ).

[0006] In one aspect, a compound having the formula (I) is provided (HLEM)z - A (I). z is an integer from 1 to 5.

[0007] In this embodiment, the half-life extension motif has the following structure [ka] k is an integer between 1 and 5.

[0008] L1 is independently a covalent linker. L2 is independently an unsubstituted alkylene. .

[0009] In this embodiment, the nucleic acid covalently binds to the incorporation motif (UM).

[0010] In this embodiment, the compound has formula (II) (HLEM)zA-(UM)t (II). t is an integer between 1 and 5.

[0011] In this embodiment, the incorporated motif independently has the following structure [ka]

[0012] L3 and L4 independently bond -N(R23)-, -O-, -S-, -C(O)- , -N(R23)C(O)-, -C(O)N(R24)-, -N(R23)C(O)N( R24)-, -C(O)O-, -OC(O)-, -N(R23)C(O)O-, -OC( O)N(R24)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O) (R25)-O-, -OP(S)(R25)-O-, -OP(O)(NR23R24 )-N-, -OP(S)(NR23R24)-N-, -OP(O)(NR23R24 )-O-, -OP(S)(NR23R24)-O-, -P(O)(NR23R24)- N-, -P(S)(NR23R24)-N-, -P(O)(NR23R24)-O-, - P(S)(NR23R24)-O-、-S-S-、 substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylene, or substituted or unsub stituted heteroarylene. Each of R23, R24, and R25 is independently hydrogen, or unsubstituted C1-C10 alkyl.

[0013] L5 is -L5A-L5B-L5C-L5D-L5E-. L6 is -L6A-L 6B-L6C-L6D-L6E-. L5A, L5B, L5C, L5D, L5E, L 6A, L6B, L6C, L6D, and L6E are independently a bond, -NH-, -O-, - S-, -C(O)-, -NHC(O)-, -NHC(O)NH-, -C(O)O-, -O ) C(O)-, -C(O)NH-, substituted or unsubstituted alkylene, substituted or unsubstituted he teroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycl oalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroary lene.

[0014] R1 and R2 are independently unsubstituted C1-C25 alkyl, and at least one of R1 and R2 is unsubstituted C9-C19 alkyl. R3 is 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 cycloalk yl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or It is a substituted or unsubstituted heteroaryl.

[0015] In one aspect, as described herein, a method is provided that includes contacting a cell with a compound or a compound comprising nucleic acid (A). A method is provided that includes administering to a subject a compound described herein or a compound comprising nucleic acid (A).

[0016] In one aspect, a compound for use in therapy or a compound comprising nucleic acid (A) as described herein is provided. A method is provided that includes administering to a subject a compound comprising nucleic acid (A) as described herein.

[0017] In one aspect, a method for introducing nucleic acid into cells within a subject is provided. The method includes administering to the subject a compound comprising nucleic acid (A) as described herein. A cell comprising a compound comprising nucleic acid (A) as described herein is provided.

[0018] In one aspect, a pharmaceutical composition is provided that includes a pharmaceutically acceptable excipient and a compound comprising nucleic acid (A) as described herein. Other aspects are disclosed below.

[0019]

[0020]

[0021]

[0022] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1A] [Figure 1B] [Figure 1C] The structure of DT-000137 according to an exemplary embodiment is shown. [Figure 1B] The structure of DT-000146 according to an exemplary embodiment is shown. [Figure 1C] The structure of DT-000347 according to an exemplary embodiment is shown. [Figure 1D] The structure of DT-000155 according to an exemplary embodiment is shown. [Figure 1E] The structure of DT-000156 according to an exemplary embodiment is shown. [Figure 1F] The structure of DT-000157 according to an exemplary embodiment is shown. [Figure 1G] The structure of DT-000272 according to an exemplary embodiment is shown. [Figure 1H] The structure of DT-000273 according to an exemplary embodiment is shown. [Figure 1I] The structure of DT-000274 according to an exemplary embodiment is shown. [Figure 1J] The structure of DT-000275 according to an exemplary embodiment is shown. [Figure 1K] The structure of DT-000276 according to an exemplary embodiment is shown. [Figure 1L] The structure of DT-000277 according to an exemplary embodiment is shown. [Figure 1M] The structure of DT-000278 according to an exemplary embodiment is shown. [Figure 1N] The structure of DT-000350 according to an exemplary embodiment is shown. [Figure 10] The structure of DT-000183 is shown. [Modes for carrying out the invention]

[0023] definition Unless otherwise defined, all technical terms, scientific terms, abbreviations, and chemical terms used herein are defined in this specification. The chemical structure and chemical formula have the same meaning as generally understood by those skilled in the art. The chemical structures and formulas described in this specification are in accordance with the standard rules of chemical valence known in the chemical field. Constructed. All patents, applications, published applications, and other publications referenced herein are constructed. Unless otherwise specified, the entirety of the works is incorporated by reference. Unless otherwise specified, mass spectrometry, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA technology, And conventional methods of pharmacology are used. Furthermore, the phrase "including" is used. The terms, as well as "include", "includes", and The use of other forms, such as "included," is not limited to this specification. When used in a transitional clause or in the body of the claims, it includes (co The terms "comprise" and "comprising" have an unrestricted meaning. It should be interpreted as having at least ~. In other words, this term means "having at least ~". "T" should be interpreted as synonymous with the phrase "at least includes." (In the context of the process) When used in this context, the term "comprising" means that the process includes This means that it includes at least the listed steps, but may include additional steps. When used in connection with compounds, compositions, or devices, the term "includes" is used. The term "ing)" means that the compound, composition, or device has the listed characteristics or This means that it includes at least the constituent elements, but may include additional features or constituent elements. ru.

[0024] If substituents are identified by those conventional chemical formulas written from left to right, then they are , which would result from writing the structure from right to left, equally include chemically identical substituents, For example, -CH2O- is equal to -OCH2-.

[0025] The term "alkyl" can refer to itself or as part of another substituent, unless otherwise specified. As long as it is a straight chain (i.e., unbranched) or branched carbon chain (or carbon), or a combination thereof This refers to a combination, which may be fully saturated, monovalent, or polyunsaturated, and can be monovalent, divalent, or divalent. It can contain valence and polyvalent radicals. Alkyls can contain a specified number of carbon atoms. (For example, C1-C10 means 1 to 10 carbon atoms). Alkyl is an acyclic chain. Examples of saturated hydrocarbon radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, methyl, and other groups, for example, n- Examples include homologs and isomers such as pentyl, n-hexyl, n-heptyl, and n-octyl. However, it is not limited to these. An unsaturated alkyl group may have one or more double or triple bonds. It has a bond. Examples of unsaturated alkyl groups include vinyl, 2-propenyl, and cyanoacrylate. Rothyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-( 1,4-pentadienyl), ethinyl, 1- and 3-propynyl, 3-butynyl, Examples include, but are not limited to, higher homologs and isomers. Alkoxys are acids This alkyl group is bonded to the rest of the molecule via an elementary linker (-O-). The part may be an alkenyl part. The alkyl part may be an alkynyl part. The alkyl portion may be completely saturated. The alkenyl has one or more double bonds in addition to It may contain more than one double bond and / or one or more triple bonds. Alkynnyl is 1 In addition to more than one triple bond, one or more triple bonds and / or one or more double bonds It may include.

[0026] In these embodiments, the term "cycloalkyl" refers to monocyclic, bicyclic, or polycyclic cycloalkyl compounds. This refers to an alkyl ring system. In the embodiment, a monocyclic ring system is a ring containing 3 to 8 carbon atoms. It is a hydrocarbon group, and such a group can be saturated or unsaturated, but it is not aromatic. In the embodiment, the cycloalkyl group is completely saturated. Examples of monocyclic cycloalkyl groups include These are cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, and cyclohexyl This includes cyclohexenyl, cycloheptyl, and cyclooctyl. The rhalkyl ring system is a crosslinked monocyclic ring or a fused bicyclic ring. In the embodiment, a crosslinked monocyclic ring The ring is a monocyclic ring with two non-adjacent carbon atoms and one to three additional carbon atoms in an alkylate. A crosslinking group (i.e., a crosslinking group of form (CH2)w, where w is 1, 2, or 3) It contains a monocyclic cycloalkyl ring linked by a crosslinking group. Typical examples include bicyclo[3.1.1]heptane and bicyclo[2.2.1]heptane. n, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3. 3.1]nonanes and bicyclo[4.2.1]nonanes are examples, but are not limited to these. It is not possible. In the embodiment, the condensed bicyclic cycloalkyl ring system is phenyl, monocyclic cycloalkyl Kill, monocyclic cycloalkenyl, monocyclic heterocyclyl, or monocyclic heteroaryl It contains a monocyclic cycloalkyl ring condensed to either of the following. In the embodiment, it is a crosslinked or condensed bicyclic ring. The cycloalkyl formula is a monocyclic cycloalkyl compound, and through any carbon atom contained within the monocyclic cycloalkyl ring, the parent It is bonded to the molecular portion. In the embodiment, the cycloalkyl group is optionally and independently oxo Alternatively, it is substituted with one or two groups, which are thia. In embodiments, a condensed bicyclic cyan Chloalkyls are monocyclic cycloalkyls with a phenyl ring, 5 or 6 members, or 5 or 6 members. Monocyclic cycloalkenyls, 5- or 6-membered monocyclic heterocyclyls, or 5 or A 5 or 6-membered monocyclic cycloaryl condensed with one of the 6-membered monocyclic heteroaryls. It is a kill ring, and is independently oxo or thia, by one or two groups, in the case Therefore, it is substituted. In the embodiment, the polycyclic cycloalkyl ring system is (i) bicyclic Aryl, bicyclic heteroaryl, bicyclic cycloalkyl, bicyclic cycloalkenyl, (ii) A ring system selected from the group consisting of bicyclic heterocyclyls, or (ii) pheny Ru, bicyclic aryl, monocyclic or bicyclic heteroaryl, monocyclic or bicyclic sic Roalkyl, monocyclic or bicyclic cycloalkenyl, and monocyclic or bicyclic heteroalkyl A monoring condensed into one of two other ring systems independently selected from the group consisting of rocyclyl. It is a cycloalkyl ring (basic ring). In the embodiment, the polycyclic cycloalkyl is the basic ring. It is bonded to the parent molecule via any carbon atom contained within. In the embodiment, a polycyclic Cycloalkyl ring systems include (i) bicyclic aryl, bicyclic heteroaryl, and bicyclic cycloalkyl rings. Selected from the group consisting of lukyl, bicyclic cycloalkenyl, and bicyclic heterocyclyl (ii) a single ring system, or (ii) phenyl, monocyclic heteroaryl, monocyclic cycloalkyl A group independently selected from the group consisting of monocyclic cycloalkenyls and monocyclic heterocyclyls. It is a monocyclic cycloalkyl ring (basic ring) fused to one of the other two ring systems. Examples of cyclic cycloalkyl groups include tetradecahydrophenantrenyl and perhydrof Examples include ethothiazine-1-yl and perhydrophenoxazine-1-yl, This is not limited to these.

[0027] In this embodiment, the cycloalkyl is a cycloalkenyl. The term is used according to its simple, ordinary meaning. In embodiments, cycloalkenyl This is a monocyclic, bicyclic, or polycyclic cycloalkenyl ring system. In the embodiment, a monocyclic cycloalkenyl ring system is used. The chloroalkenyl ring system is a cyclic hydrocarbon group containing 3 to 8 carbon atoms, and such a group It is unsaturated (i.e., contains at least one cyclic carbon-carbon double bond), but aromatic. No. Examples of monocyclic cycloalkenyl ring systems include cyclopentenyl and cyclohe Xenyl is one example. In the embodiment, the bicyclic cycloalkenyl ring is a bridged monocyclic ring, or is a condensed bicyclic ring. In the embodiment, the bridging monocyclic ring is two adjacent monocyclic rings Alkylene bridges between 1-3 additional carbon atoms (i.e., form (CH)) 2) A monoring bonded by a bridging group of w, where w is 1, 2, or 3. It contains a cycloalkenyl ring. A typical example of a bicyclic cycloalkenyl is norbol. Examples include, but are not limited to, nenyle and bicyclo[2.2.2]octo2enyl. No. In the embodiment, the condensed bicyclic cycloalkenyl ring system is phenyl, monocyclic cycloal Kill, monocyclic cycloalkenyl, monocyclic heterocyclyl, or monocyclic heteroaryl It contains a monocyclic cycloalkenyl ring condensed in either way. In the embodiment, it is bridged or condensed in either way. Cycloalkenyls are monocyclic cycloalkenyls that have any carbon atom contained within the monocyclic cycloalkenyl ring It is bonded to the parent molecule. In the embodiment, the cycloalkenyl group is optionally and independently Substituted with one or two groups, which are oxo or thia. In embodiments, polycyclic Cycloalkenyl rings include (i) bicyclic aryl, bicyclic heteroaryl, and bicyclic cycloalkenyl rings. Selected from the group consisting of lukyl, bicyclic cycloalkenyl, and bicyclic heterocyclyl (ii) a single ring system, or (ii) phenyl, bicyclic aryl, monocyclic or bicyclic hetero Aryl, monocyclic or bicyclic cycloalkyl, monocyclic or bicyclic cycloalkene Two independently selected groups consisting of a ru and a monocyclic or bicyclic heterocyclil. It contains a monocyclic cycloalkenyl ring (basic ring) fused to one of the following ring systems. In the embodiment, Polycyclic cycloalkenyls can connect to the parent molecule via any carbon atom contained within the base ring. They are bonded. In the embodiment, the polycyclic cycloalkenyl ring is (i) a bicyclic aryl, and Cyclic heteroaryls, bicyclic cycloalkyls, bicyclic cycloalkenyls, and bicyclic he (ii) a ring system selected from the group consisting of telocyclyl, or (ii) phenyl, monocyclic he Teloaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, and monocyclic heteroalkyl Monocyclic cyclos condensed into one of two ring systems independently selected from the group consisting of krills It contains an alkenyl ring (basic ring).

[0028] In the embodiments, the heterocycloalkyl is a heterocyclyl. In this context, the term "heterocyclyl" refers to monocyclic, bicyclic, or polycyclic heterocyclic rings. Heterocyclyl monocyclic heterocycles are monocyclic heterocycles where the ring is saturated or unsaturated but not aromatic. It includes at least one heteroatom independently selected from the group consisting of , N, and S, It is a 3, 4, 5, 6, or 7-membered ring. The 3 or 4-membered ring consists of O, N, and S. It contains one heteroatom selected from the group. The 5-membered ring has 0 or 1 double bond and It contains one, two, or three heteroatoms selected from the group consisting of O, N, and S. It is possible. A 6 or 7-membered ring may have 0, 1, or 2 double bonds and from O, N, and S. It may contain one, two, or three heteroatoms selected from the group. Heterocycline A monocyclic heterocycle is any carbon atom contained within a heterocyclic heterocycle or any carbon atom. It is connected to the parent molecule via a nitrogen atom. Heterocyclyl monocyclic heterocyclic Typical examples include azetidinil, azepanil, aziridinil, diazepanil, and 1,3-diozhe. Xanil, 1,3-dioxolanil, 1,3-dithiolanil, 1,3-dithianil, Imi Dazolinil, imidazolidinil, isothiazolinil, isothiazolinil, isoxazoli Nyl, isoxazolidinyl, morpholinyl, oxadiazolinyl, oxadiazolidinyl , oxazolinyl, oxazolidinyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl Linyl, pyrazolidinyl, pyrrolinyl, pyrrolinyl, tetrahydrofuranyl, tetrahi Dorothienyl, thiadiazolinyl, thiadiazolidinyl, thirazolinyl, thiazolidinyl , thiomorpholinyl, 1,1-dioxidethiomorpholinyl (thiomorpholin sulfone) This includes, but is not limited to, thiopyranil and trithianil. The lyl bicyclic heterocycle includes phenyl, monocyclic cycloalkyl, monocyclic cycloalkenyl, and monocyclic cycloalkyl. It is a monocyclic heterocycle condensed into either a cyclic heterocycle or a monocyclic heteroaryl. A heterocyclyl bicyclic heterocycle is any heterocycle contained within the monocyclic heterocycle portion of a bicyclic ring system. It is connected to the parent molecule via a carbon atom or any nitrogen atom. Bicyclic heterozygous Typical examples of krill include, but are not limited to, 2,3-dihydrobenzofuran-2-yl, 2,3 Dihydrobenzofuran 3-yl, indoline 1-yl, indoline 2-yl, indoline 3-yl , 2,3-dihydrobenzothiene 2-yl, decahydroquinolinyl, decahydroisoquinolinyl It contains octahydro-1H-indolyl and octahydrobenzofuranil. Morphologically, the heterocyclyl group is optionally, independently, oxo or thia, one or It is substituted with two groups. In a particular embodiment, the bicyclic heterocyclil is phenyl A ring, a 5- or 6-membered monocyclic cycloalkyl, a 5- or 6-membered monocyclic cycloalkene A monocyclic heterocyclyl with 5 or 6 members, or a monocyclic heterocyclyl with 5 or 6 members. A monocyclic heterocyclyl ring of 5 or 6 members condensed with a ring, and which can be any and independently formed. Substituted by one or two groups, which are xo or thia. Polycyclic heterocycline The lyl ring system includes (i) bicyclic aryl, bicyclic heteroaryl, bicyclic cycloalkyl, and 2 A ring selected from the group consisting of cyclic cycloalkenyls and bicyclic heterocyclyls. (ii) phenyl, bicyclic aryl, monocyclic or bicyclic heteroaryl, Monocyclic or bicyclic cycloalkyls, monocyclic or bicyclic cycloalkenyls, and Two other ring systems independently selected from the group consisting of monocyclic or bicyclic heterocyclils. It is a monocyclic heterocyclyl ring (basic ring) condensed into one of the following. It is bonded to the parent molecule via any carbon or nitrogen atom contained within the base ring. In the embodiment, the polycyclic heterocyclyl ring system is (i) a bicyclic aryl, bicyclic hetero Aryl, bicyclic cycloalkyl, bicyclic cycloalkenyl, and bicyclic heterocyclic (ii) a ring system selected from the group consisting of (ii) phenyl, monocyclic heterozygous From monocyclic cycloalkyls, monocyclic cycloalkenyls, and monocyclic heterocyclines Monocyclic heterocyclines condensed into one of two other ring systems independently selected from the group. It is a cyclic ring (basic ring). An example of a polycyclic heterocyclyl group is 10H-phenothiazine. -10-yl, 9,10-dihydroacridin-9-yl, 9,10-dihydroacridin 10-yl, 10H-phenoxazine-10-yl, 10,11-dihydro-5H- Dibenzo[b,f]azepine-5-yl, 1,2,3,4-tetrahydropyrid[4,3 -g]Isoquinoline-2-yl, 12H-benzo[b]phenoxazine-12-yl, Examples include dodecahydro-1H-carbazole-9-yl, but are not limited to these. stomach.

[0029] The term "alkylene" is used either by itself or as part of another substituent, unless otherwise specified. Unless otherwise specified, it means a divalent radical derived from an alkyl group, and is not limited to -CH2C. Exemplify by H2CH2CH2-, typically an alkyl (or alkylene) group. In this specification, groups having 1 to 24 carbon atoms, and 10 or fewer carbon atoms, are preferred. "Lower alkyl" or "lower alkylene" generally has eight or fewer carbon atoms. It is a short-chain alkyl or alkylene group. The term "alkenylene" is itself Unless otherwise specified, divalent ions derived from alkenes are used either in whole or as part of another substituent. It means "jical".

[0030] The term "heteroalkyl" is used by itself or in combination with other terms, unless otherwise specified. Unless otherwise specified, at least one carbon atom and at least one heteroatom (e.g., O, Stable linear or branched chains, or combinations thereof, containing N, S, Si, or P This means that the nitrogen and sulfur atoms may be optionally oxidized, and the nitrogen heteroatom is , can be arbitrarily quaternized. Heteroatoms (e.g., O, N, S, Si, or P) are heteroatoms. Any internal position of the L-alkyl group or at any position where the alkyl group is bonded to the rest of the molecule They may be arranged in this manner. Heteroalkyls are non-cyclized chains. An example is -CH2-C H2-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 Examples include, but are not limited to, -O-CH2-CH3 and -CN. up to two such groups, including -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. Or, three heteroatoms can be consecutive. The heteroalkyl portion consists of one heteroatom (for example) It may contain O, N, S, Si, or P. The heteroalkyl portion consists of two optional elements. It may contain different heteroatoms (e.g., O, N, S, Si, or P). The kill portion consists of three arbitrarily different heteroatoms (e.g., O, N, S, Si, or P) It may contain. The heteroalkyl portion consists of four arbitrarily distinct heteroatoms (e.g., O, N). It may contain , S, Si, or P. The heteroalkyl portion consists of 5 arbitrarily different he(s). It may contain a heteroalkyl atom (e.g., O, N, S, Si, or P). It contains up to eight arbitrarily different heteroatoms (e.g., O, N, S, Si, or P). However, this is also acceptable. The term "heteroalkenyl" can be used alone or in combination with another term. Unless otherwise specified, this means a heteroalkyl group containing at least one double bond. A heteroalkenyl has one or more double bonds in addition to more than one double bond and / or 1 It may optionally contain one or more triple bonds. The term "heteroalkynyl" alone is, Or, in combination with another term, unless otherwise specified, it includes at least one triple bond. It means heteroalkyl. A heteroalkynyl has one or more triple bonds in addition to one It may optionally contain a supertriple bond and / or one or more double bonds.

[0031] Similarly, the term "heteroalkylene" can refer to a heteroalkylene that is either by itself or as part of another substituent. Unless otherwise specified, this refers to a divalent radical derived from a heteroalkyl group, and is not limited to... However, -CH2-CH2-S-CH2-CH2- and -CH2-S-CH2-CH This is exemplified by 2-NH-CH2-. For heteroalkylene groups, the heteroatom is Furthermore, it may occupy one or both ends of the chain (e.g., alkylene oxy, alkyl (e.g., dioxy, alkyleneamino, alkylenediamino). Furthermore, alkylene And in the case of heteroalkylene linking groups, the orientation of the linking group is determined by the direction in which the formula of the linking group is written. This is not implied. For example, the formula -C(O)2R'- implies -C(O)2R'- and -R' It represents both C(O)2-. As stated above, heteroalkyl groups used herein are -C(O)R', -C(O)NR', ​​-NR'R'', -OR', -SR', and / ma This includes groups such as -SO2R', which are bonded to the rest of the molecule via heteroatoms. After a list of "heteroalkyls," a specific heteroalkyl group is listed, for example, -NR'R''. When such terms are listed, the terms heteroalkyl and -NR'R'' may be redundant but mutual It will be understood that they are not exclusive. Rather, certain heteroalkyl groups are used for clarification. Enumerated. Therefore, the term "heteroalkyl" in this specification refers to specific It should not be interpreted as excluding heteroalkyl groups, such as -NR'R''. stomach.

[0032] The terms "cycloalkyl" and "heterocycloalkyl" are used either by themselves or In combination with other terms, unless otherwise specified, "alkyl" and "heteroalkyl" are used respectively. It means the cyclic version of "cycloalkyl". Cycloalkyl and heterocycloalkyl are It is not aromatic. In addition, in the case of heterocycloalkyl, the heteroatom is the heterocycle of the molecule. It can occupy the remaining bonded position. An example of a cycloalkyl group is cyclopropyl. Cyclobutyl, Cyclopentyl, Cyclohexyl, 1-Cyclohexenyl, 3-Cyclo Examples include lohexenyl and cycloheptyl, but are not limited to these. Examples of tetrahydropyridyl groups include 1-(1,2,5,6-tetrahydropyridyl) and 1-piperyl. Dinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, Tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrotiene 2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl, etc. These include, but are not limited to, "cycloalkylenes" and "heterocycloalkylenes." "Kilene" can be used alone or as part of another substituent, respectively, as cycloalkyl and This refers to a divalent radical derived from a heterocycloalkyl group.

[0033] The term "halo" or "halogen" can be used alone or as part of another substituent. Unless otherwise specified, this refers to fluorine, chlorine, bromine, or iodine atoms. Terms such as "haloalkyl" include monohaloalkyl and polyhaloalkyl. It has a taste. For example, the term "halo(C1-C4)alkyl" refers to fluoromethyl , difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chloromethyl Examples include, but are not limited to, robutyl and 3-bromopropyl.

[0034] The term "acyl" means -C(O)R unless otherwise specified, where R is a substitution. or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl Roalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, Alternatively, it is a substituted or unsubstituted heteroaryl.

[0035] The term "aryl" refers to polyunsaturated, aromatic, hydrocarbon compounds unless otherwise specified. This refers to a compound, which is either a single ring or condensed together (i.e., a condensed ring). It may be a fused ring aryl or a polycyclic (preferably 1 to 3 rings) formed by covalent bonding. This refers to a group of fused rings in which at least one of the fused rings is an aryl ring. The term "heteroaryl" refers to a group of at least one heteroaryl such as N, O, or S. This refers to an aryl group (or ring) containing nitrogen atoms, where the nitrogen and sulfur atoms are optionally oxidized. Elementary atoms can be arbitrarily quaternized. Therefore, the term "heteroaryl" is used to describe fused rings. A teloaryl group (that is, at least one of the fused rings is an aromatic heterocycle) It contains multiple rings that are condensed together. 5,6-Fused heteroarylenes are those in which one of the rings has 5 members. The other ring has 6 members, and at least one of the rings is a heteroaryl ring, together It refers to two fused rings. Similarly, in 6,6-fused ring heteroarylenes, one ring is One ring has 6 members, the other ring has 6 members, and at least one ring is a heteroaryl ring. It refers to two rings that are fused together. Also, a 6,5-fused ring heteroarylene is one of the rings. One ring has 6 members, the other ring has 5 members, and at least one of the rings is a heteroaryl ring. It refers to two rings that are fused together. A heteroaryl group is a carbon atom or heteroatom. They can be bonded to the rest of the molecule via the non-aryl and heteroaryl groups. Limited examples include phenyl, naphthyl, pyrrolyl, pyrazolyl, pyridazinyl, and tri Azinyl, pyrimidinyl, imidazolyl, pyrazinyl, prinyl, oxazolyl, iso Xazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl , benzoxazolyl, benzimidazolyl, benzofuran, isobenzofuranyl, ing Drill, isoindolyl, benzothiophenyl, isoquinolyl, quinoxalinyl, quinoli Lu, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3- Pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-o Xazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-Isoxazolyl, 4-Isoxazolyl, 5-Isoxazolyl, 2-Thiazolyl , 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thie Nyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-Benzothiazolyl, prinyl, 2-benzimidazolyl, 5-indolyl, 1-iso Quinoryl, 5-Isoquinolyl, 2-Quinoxalinyl, 5-Quinoxalinyl, 3-Quinolyl Examples include , and 6-quinolyl. Each of the above aryl ring systems and heteroaryl ring systems The substituents for each are selected from the group of permissible substituents listed below. " and "heteroarylene" can be used alone or as part of another substituent, respectively. This refers to divalent radicals derived from aryl and heteroaryl groups. The substituent may be -O-bonded to the ring heteroatom nitrogen.

[0036] A spirocyclic ring is a ring consisting of two or more rings that are bonded together by a single atom. The individual rings within a spirocyclic ring may be identical or different. Each ring may be substituted or unsubstituted, and each individual ring within a set of spiro rings It may have different substituents. Possible substituents of individual rings within a spirocyclic ring are spiro If it is not part of a cyclic ring, then a possible substituent on the same ring (e.g., a cycloalkyl ring or a hematologic ring) It is a substituent on a telocycloalkyl ring. The spirocyclic ring is a substituted or unsubstituted cycloalkyl ring. Lukyl, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene The group may be a substituted or unsubstituted heterocycloalkylene, or a spirocyclic ring group Each ring within is one type of ring (for example, all rings are substituted heterocycloalkylates). A straight line containing a heterocycloalkylene in which each ring may be the same or different substituted heterocycloalkylene. It could be any of the items in the previous list. When referring to a spiro-ring system, a complex ring is used. A formula spiro ring is a ring in which at least one ring is a heterocyclic ring, and each ring can be a different ring. This refers to a spirocyclic ring. When referring to a spirocyclic ring system, substitutional spirocyclic rings are few. This means that at least one ring is substituted, and each substituent can be arbitrarily different. do.

[0037] symbol [ka] The symbol indicates the bonding point of a chemical part to the rest of a molecule or chemical formula.

[0038] As used herein, the term "oxo" refers to oxygen double-bonded to a carbon atom. It tastes good.

[0039] It is covalently bonded to the alkylene moiety (also referred to herein as the alkylene linker). The term "alkylarylene" refers to the arylene portion. In the embodiment, alkyl The leylene group has the following formula [ka]

[0040] The alkyl arylene portion is an alkylene portion or an arylene linker (for example, carbon (Elements 2, 3, 4, or 6), halogen, oxo, -N3, -CF3, -CCl3, -C Br3, -CI3, -CN, -CHO, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO2CH3, -SO3H, -OSO3H, -SO2NH2, - NHNH2, -ONH2, -NHC(O)NHNH2, substituted or unsubstituted C1-C5 (For example, by substituents) It may be substituted. In this embodiment, the alkylarylene is unsubstituted.

[0041] The above terms (for example, "alkyl", "heteroalkyl", "cycloalkyl", "heteroalkyl") Each of the following is indicated: Includes both substituted and unsubstituted forms of radicals. Preferred substituents for each type of radical. The following is provided.

[0042] Alkyl and heteroalkyl radicals (often alkylene, alkenyl, hetero Alkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, (including those groups referred to as cycloalkenyls and heterocycloalkenyls) The substituents are 0 to (2m'+1) (where m' is the carbon atom in such radicals) The total number is a number within a range, not limited to -OR', =O, =NR', =N-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)2 R', -NR-C(NR'R''R''')=NR'''', -NR-C(NR'R'' )=NR''', -S(O)R', -S(O)2R', -S(O)2NR'R'', -N RSO2R', -NR'NR''R''', -ONR'R'', -NR'C(O)NR' 'NR'''R''', -CN, -NO2, -NR'SO2R'', -NR'C(O) A variety of bases can be selected from R'', -NR'C(O)-OR'', -NR'OR''. It can be one or more of these. R, R', R'', R''', and R'''' are each preferred. Alternatively, hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cyclo Alkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl (example) For example, aryls substituted with 1 to 3 halogens, substituted or unsubstituted heteroaryls , substituted or unsubstituted alkyl, alkoxy, or thioalkoxy groups, or Alley This refers to an R alkyl group. If a compound described herein contains more than one R group, for example, R Each of the groups is such that when there is one more than one of these groups, each R', R'', R''', and R' '''Independently selected as a group. R' and R'' are bonded to the same nitrogen atom. In some cases, it may combine with a nitrogen atom to form a 4, 5, 6, or 7-membered ring. For example -NR'R'' includes 1-pyrrolidinil and 4-morpholinil, but these Not limited to this. From the above discussion of substituents, a person skilled in the art would know that "alkyl" The terms include haloalkyl (e.g., -CF3 and -CH2CF3) and acyl (e.g., For example, hydrogen in -C(O)CH3, -C(O)CF3, -C(O)CH2OCH3, etc. It is intended to include groups that contain carbon atoms bonded to groups other than the group. It is likely.

[0043] Similar to the substituents described for alkyl radicals, aryl and heteroaryl groups The substituents for this change, for example, the number of atoms on the aromatic ring system ranging from 0 to the total number of open valencies. In this context, -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)2 NR'R'', -NRSO2R', -NR'NR''R''', -ONR'R'', -N R'C(O)NR''NR'''R'''', -CN, -NO2, -R', -N3, -C H(Ph)2, fluoro(C1-C4)alkoxy, fluoro(C1-C4)alkyl, -NR'SO2R'', -NR'C(O)R'', -NR'C(O)-OR'', -NR 'OR', selected from, in the expression, R', R'', R''', and R'''' are preferred. Alternatively, hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted heteroalkyl groups, or hydrogen, substituted or unsubstituted heteroalkyl groups. , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, The selection is made from substituted or unsubstituted aryls, and substituted or unsubstituted heteroaryls. If the compounds described herein contain more than one R group, for example, each of the R groups is one of these When there is one more than one group, each R', R'', R''', and R'''' group is independent. It is selected.

[0044] Rings (e.g., cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cy (Chloalkylene, heterocycloalkylene, arylene, or heteroarylene) Substituents are substituents on the ring (generally called floating substituents), rather than on specific atoms of the ring. This can be shown. In such cases, the substituent is a ring atom (according to the rules of chemical valence). It may be bonded to either of the following, and in the case of a fused ring or a spirocyclic ring, the fused ring or spiro A substituent shown as being bonded to a member of a cyclic ring (a floating substituent on a monocycle) is a fused ring. Alternatively, the substituent may be a substituent on any of the spirocyclic rings (a floating substituent on a polycyclic ring). It is bonded to a ring rather than a specific atom (floating substituent), and the subscript of the substituent is greater than 1. If the value is an integer, multiple substituents can be the same atom, the same ring, different atoms, different fused rings, or different atoms. The substituents may be on a spirocyclic ring, and each substituent may be arbitrarily different. The rest of the molecule If the bonding points of the ring are not limited to a single atom (floating substituent), the bonding points are limited to the bonding points of the ring. It may be any atom, and in the case of a fused ring or spirocyclic ring, according to the rules of chemical valency It may be any atom of either a fused ring or a spirocyclic ring. , or a spirocyclic ring containing one or more ring heteroatoms, a ring, a fused ring, or a spirocyclic ring The ring has another floating substituent (including, but not limited to, a bond site to the rest of the molecule). When shown together, the floating substituent may be bonded to the heteroatom. In a structure or formula having a free substituent, it is shown that one or more hydrogens are bonded to it. Compound (for example, a ring nitrogen having two bonds to a ring atom and a third bond to hydrogen), hetero When an atom is bonded to a floating substituent, the substituent, according to the rules of chemical valence, places hydrogen in the atom. It will be understood if you change it.

[0045] Two or more substituents are arbitrarily joined to form aryl, heteroaryl, cycloalkyl, and Alternatively, a heterocycloalkyl group may be formed. Such so-called ring-forming substituents are not necessary. While not always the case, it is typically observed in a form bonded to a ring-shaped base structure. In one embodiment, The ring-forming substituents are bonded to adjacent members of the base structure. For example, adjacent to the cyclic base structure Two ring-forming substituents bonded to adjacent members form a fused ring structure. Another embodiment In this case, the ring-forming substituent is bonded to a single member of the base structure. For example, the cyclic base structure Two ring-forming substituents bonded to a single member create a spirocyclic structure. In this embodiment, the ring-forming substituent is bonded to a non-adjacent member of the base structure.

[0046] Two of the substituents on adjacent atoms of an aryl or heteroaryl ring may optionally be The ring of formula -TC(O)-(CRR')qU- may be formed, where T and U are independent. The following are possible combinations: -NR-, -O-, -CRR'-, or single joins, where 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 substituted with substituents of the formula -A-(CH2)rB-, where A and B is independent of -CRR'-, -O-, -NR-, -S-, -S(O)-, -S(O)2 -, -S(O)2NR'-, or a simple associativity where 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 an aryl ring or heteroaryl ring are: Optionally, substitutions of the substituents of the formula -(CRR')s-X'-(C''R''R''')d- are used. It is also fine that s and d are independent integers from 0 to 3, and X' is -O-, -NR'-, The substituent R is -S-, -S(O)-, -S(O)2-, or -S(O)2NR'-. R', R'', and R'''' are preferably independently hydrogen, substituted or unsubstituted aluminum. Kill, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or Unsubstituted heterocycloalkyls, substituted or unsubstituted aryls, and substituted or unsubstituted heterocycloalkyls Selected from the Royril series.

[0047] As used herein, the terms “heteroatom” or “ring heteroatom” refer to an acid It means that it contains element (O), nitrogen (N), sulfur (S), phosphorus (P), and silicon (Si). It tastes good.

[0048] As used herein, “substituent” means a group selected from the following parts: (A) Oxo, halogen, -CF3, -CCl3, -CBr3, -CI3, -CHF2 , -CHCl2, -CHBr2, -CHI2, -CH2F, -CH2Cl, -CH2Br , -CH2I, -CN, -N3, -OH, -NH2, -COOH, -CONH2, -NO 2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, -NHNH2, - ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NH C(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCl3, -OCBr 3, -OCI3, -OCHF2, -OCHCl2, -OCHBr2, -OCHI2, -O CH2F, -OCH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl (e.g., (C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heterozygotes Alkyl (for example, 2-8 member heteroalkyl, 2-6 member heteroalkyl, or 2-4 member) Heteroalkyls), unsubstituted cycloalkyls (e.g., C3-C8 cycloalkyls, C3- C6 cycloalkyl (or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (For example, 3-8 member heterocycloalkyl, 3-6 member heterocycloalkyl, or 5- 6-membered heterocycloalkyls), unsubstituted aryls (e.g., C6-C10 aryls, C10 (aryl or phenyl), or unsubstituted heteroaryl (e.g., 5-10 member hetero) Aryl, 5-9 member heteroaryl, or 5-6 member heteroaryl), and (B) Alkyl, heterozygous, substituted with at least one substituent selected from the following: Roalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl: (i) Oxo, halogen, -CF3, -CCl3, -CBr3, -CI3, -CHF 2, -CHCl2, -CHBr2, -CHI2, -CH2F, -CH2Cl, -CH2B r, -CH2I, -CN, -N3, -OH, -NH2, -COOH, -CONH2, -N O2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -N HC(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCl3, -OCB r3, -OCI3, -OCHF2, -OCHCl2, -OCHBr2, -OCHI2, - OCH2F, -OCH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl (e.g.) (C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted hete Roalkyl (e.g., 2-8 member heteroalkyl, 2-6 member heteroalkyl, or 2-4 member heteroalkyl) (C3-C8 cycloalkyl, C3) -C6 cycloalkyl (or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (For example, 3-8 member heterocycloalkyl, 3-6 member heterocycloalkyl, or 5 ~6-membered heterocycloalkyls), unsubstituted aryls (e.g., C6-C10 aryls, C1 0 aryls, or phenyls, or unsubstituted heteroaryls (e.g., 5-10 member heteroaryls) Roaryls, 5-9 member heteroaryls, or 5-6 member heteroaryls), and (ii) alkyl, which is substituted with at least one substituent selected from the following Heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl: (a) Oxo, halogen, -CF3, -CCl3, -CBr3, -CI3, -CH F2, -CHCl2, -CHBr2, -CHI2, -CH2F, -CH2Cl, -CH2 Br, -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, -OC Br3, -OCI3, -OCHF2, -OCHCl2, -OCHBr2, -OCHI2, -OCH2F, -OCH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl (for example) (C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted he Telothermic (e.g., 2-8 member heteroalkyl, 2-6 member heteroalkyl, or 2- 4-membered heteroalkyls), unsubstituted cycloalkyls (e.g., C3-C8 cycloalkyls, C 3-C6 cycloalkyl (or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl Kill (for example, 3-8 member heterocycloalkyl, 3-6 member heterocycloalkyl, or 5-6 member heterocycloalkyls), unsubstituted aryls (e.g., C6-C10 aryls, C 10-aryl or phenyl compounds, or unsubstituted heteroaryl compounds (e.g., 5-10 member heteroaryl compounds) Teloaryls (5-9 member heteroaryls, or 5-6 member heteroaryls), and (b) alkyl, hetero, substituted with at least one group selected from the following: Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl:oxo , 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, -N HC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, - NHC(O)OH, -NHOH, -OCF3, -OCCl3, -OCBr3, -OCI3 , -OCHF2, -OCHCl2, -OCHBr2, -OCHI2, -OCH2F, -O CH2Cl, -OCH2Br, -OCH2I, unsubstituted alkyl (e.g., C1-C8 alkyl) Kill, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (for example) For example, 2-8 member heteroalkyl, 2-6 member heteroalkyl, or 2-4 member heteroalkyl ), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl) Kill, or C5-C6 cycloalkyl, unsubstituted heterocycloalkyl (e.g., 3- 8-membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl (C6-C10 aryl, C10 aryl, and (phenyl), or unsubstituted heteroaryls (e.g., 5-10 member heteroaryls, 5- (9-membered heteroaryl, or 5-6 membered heteroaryl).

[0049] The term "size-limited substituent" as used herein refers to a size-limited substituent. "substituent)" or "size-limited substituent (size-limited substituent)" refers to "substituent" This means a group selected from all the substituents mentioned above, and each substituted or unsubstituted alkyl is They are substituted or unsubstituted C1-C20 alkyl groups, and each substituted or unsubstituted heteroalkyl group is Each is a substituted or unsubstituted 2-20 member heteroalkyl group, and each is a substituted or unsubstituted cycloalkyl group. These are substituted or unsubstituted C3-C8 cycloalkyls, and each substituted or unsubstituted heteroalkyl Roalkyls are substituted or unsubstituted 3- to 8-membered heterocycloalkyls, each substituted or unsubstituted Substituting aryls are substituted or unsubstituted C6-C10 aryls, and each substituted or unsubstituted aryl Terroraryls are substituted or unsubstituted 5- to 10-membered heteroaryls.

[0050] As used herein, “lower substituent” or "Lower substituent group" is a term that replaces "substituent". This refers to a group selected from all the substituents mentioned above, and each substituted or unsubstituted alkyl group is a substituted or unsubstituted C1-C8 alkyl group, and each substituted or unsubstituted heteroalkyl group is , substituted or unsubstituted 2-8 member heteroalkyls, each substituted or unsubstituted cycloalkyl These are substituted or unsubstituted C3-C7 cycloalkyls, and each substituted or unsubstituted heteroalkyl Roalkyls are substituted or unsubstituted 3- to 7-membered heterocycloalkyls, each substituted or unsubstituted Substituting aryls are substituted or unsubstituted C6-C10 aryls, and each substituted or unsubstituted aryl Terroraryls are substituted or unsubstituted 5- to 9-membered heteroaryls.

[0051] In the embodiment, substituted or unsubstituted moieties (for example, substituted or unsubstituted alkyl groups, substituted or unsubstituted alkyl groups) are also used. Alternatively, unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted Heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl , substituted or unsubstituted alkylenes, substituted or unsubstituted heteroalkylenes, substituted or is an unsubstituted cycloalkylene, a substituted or unsubstituted heterocycloalkylene, a substituted or Unsubstituted arylenes, and / or substituted or unsubstituted heteroarylenes, are unsubstituted. (For example, unsubstituted alkyl, unsubstituted heteroalkyl, and unsubstituted cycloalkyl, respectively) , unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted aryl Chelen, unsubstituted heteroalkylene, unsubstituted cycloalkylene, unsubstituted heterocycloalkyl (These are arylene, unsubstituted arylene, and / or unsubstituted heteroarylene). In embodiments This refers to the substituted or unsubstituted portion (for example, a substituted or unsubstituted alkyl group, a substituted or unsubstituted group). Heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclo Alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted k is an unsubstituted alkylene, a substituted or unsubstituted heteroalkylene, or a substituted or unsubstituted alkylene. Roalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted Ally Len, and / or substituted or unsubstituted heteroarylenes, are substitutions (e.g., Each of these: substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocyclo Alkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene substituted cycloalkylenes, substituted heterocycloalkylenes, substituted arylenes, and / or (This is a substituted heteroarylene.)

[0052] In the embodiment, the substituted portion (for example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl) Lukyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkyl , substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted Arylenes (and / or substituted heteroarylenes) are substituted with at least one substituent. Furthermore, if the substituted portion is substituted with multiple substituents, each substituent is arbitrarily different. This is also acceptable. In the embodiment, if the substituted portion is replaced by multiple substituents, each substituent is different.

[0053] In the embodiment, the substituted portion (for example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl) Lukyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkyl , substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted Arylenes and / or substituted heteroarylenes) have at least one size limitation When a substitution is made and the substituted portion is replaced by multiple size-limited substituents, each size-limited The constant substituents may be arbitrarily different. In the embodiment, the substitution portion has multiple size limiting properties. When substitution occurs, each size-restricting substituent is different.

[0054] In the embodiment, the substituted portion (for example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl) Lukyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkyl , substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted Arylenes (and / or substituted heteroarylenes) are substituted with at least one lower substituent. If a substitution occurs and the substituted portion is replaced by multiple lower substituents, each lower substituent may be They may be different. In the embodiment, if the substituted portion is substituted with multiple lower substituents, each Lower substituents are different.

[0055] In the embodiment, the substituted portion (for example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl) Lukyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkyl , substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted Arylenes (and / or substituted heteroarylenes) are composed of at least one substituent, cy Substituted with size-limited substituents or lower substituents, the substituted portion is a substituent, size-limited substituent, And if substituted with multiple groups selected from lower substituents, each substituent, size limited The substituents and / or lower substituents may be arbitrarily different. In the embodiment, substitutions The portion is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents. If so, each substituent, size-limiting substituent, and / or lower substituent is different.

[0056] In the embodiments of the compounds described herein, each substituted or unsubstituted alkyl is substituted (for example, (substituted with substituents, size-limited substituents, or lower substituents), or unsubstituted C1-C2 It can be alkyl, and each substituted or unsubstituted heteroalkyl can be substituted (e.g., substituent, (Substituted with size-limited substituents or lower substituents), or unsubstituted 2- to 20-membered ring heterozygotes It is an alkyl group, and each substituted or unsubstituted cycloalkyl group is a substituted (e.g., substituent, cycloalkyl) (Substituted with a limited substituent or a lower substituent), or unsubstituted C3-C8 cycloalkyl Each substituted or unsubstituted heterocycloalkyl is a substituted (e.g., substituent, cy (substituted with limited substituents or lower substituents), or unsubstituted 3- to 8-membered ring heterocyclo The alkyl group is an alkyl group, and each or unsubstituted aryl group is substituted (e.g., substituent, size-limited substitution). If it is a group (substituted with a lower substituent) or an unsubstituted C6-C10 aryl, then Each substituted or unsubstituted heteroaryl is a substitution (e.g., substituent, size (Substituted with limited substituents or lower substituents), or unsubstituted 5-10 membered ring heteroary In the embodiments described herein, each substituted or unsubstituted alkylene is substituted (for example). (substituted with substituents, size-limited substituents, or lower substituents), or unsubstituted C1-C 20 alkylenes, and each substituted or unsubstituted heteroalkylene is substituted (for example, substituted (substituted with a group, size-limited substituent, or lower substituent), or an unsubstituted 2-20 member ring It is a teloalkylene, and each substituted or unsubstituted cycloalkylene is substituted (for example, substituted (substituted with a group, size-limited substituent, or lower substituent), or unsubstituted C3-C8 group Each heterocycloalkylene is a substituted or unsubstituted heterocycloalkylene (for example, Substituting with substituents, size-limited substituents, or lower substituents, or unsubstituted 3- to 8-membered rings It is a heterocycloalkylene, and each substituted or unsubstituted arylene is substituted (for example, substituted (substituted with substitution groups, size-limited substituents, or lower substituents), or unsubstituted C6-C10 It is an arylene, and / or each substituted or unsubstituted heteroarylene is a substituted (For example, substituted with substituents, size-restricted substituents, or lower substituents), or unsubstituted. It is a 5-10 membered ring heteroarylene.

[0057] In the embodiment, each substituted or unsubstituted alkyl is substituted (e.g., substituent, size limit) It is a substituent (substituted with a lower substituent) or an unsubstituted C1-C8 alkyl, and each Substituted or unsubstituted heteroalkyls are substituted (e.g., substituents, size-limited substituents, and (which is substituted with a lower substituent), or an unsubstituted 2- to 8-membered ring heteroalkyl, and each substitution is Alternatively, unsubstituted cycloalkyls may have substitutions (e.g., substituents, size-limited substituents, or lower substituents). (substituted with substituents) or unsubstituted C3-C7 cycloalkyl, each substituted or Unsubstituted heterocycloalkyls are substituted (e.g., substituents, size-limited substituents, or lower substituents). It is a substituted (or unsubstituted) or unsubstituted 3- to 7-membered ring heterocycloalkyl, and each substitution is Alternatively, unsubstituted aryls are substituted (e.g., substituents, size-limited substituents, or lower substituents). (which are replaced by), or are unsubstituted C6-C10 aryls, and / or each substitution Alternatively, unsubstituted heteroaryls may be substituted (e.g., substituents, size-limited substituents, or low It is a heteroaryl ring (substituted with a quaternary substituent) or an unsubstituted 5- to 9-membered ring heteroaryl. In the embodiment, Each substituted or unsubstituted alkylene is substituted (e.g., substituents, size-limited substituents, and (is substituted with a lower substituent) or is an unsubstituted C1-C8 alkylene, and each substitution or Unsubstituted heteroalkylenes are substituted (e.g., substituents, size-limited substituents, or lower substituents). (Substituted by substitution groups) or unsubstituted 2-8 membered ring heteroalkylenes, each substitution or Unsubstituted cycloalkylenes are substituted (e.g., substituents, size-limited substituents, or lower substitutions). (substituted with a group), or unsubstituted C3-C7 cycloalkylene, each substituted or unsubstituted Substituted heterocycloalkyls are substituted or unsubstituted 3- to 7-membered heterocycloalkyls. Each substituted or unsubstituted arylene is substituted (e.g., substituents, size-limited substituents, and (is substituted with a lower substituent), or is an unsubstituted C6-C10 arylene, as well as / Alternatively, each substituted or unsubstituted heteroarylene may be substituted (e.g., substituent, size limited). Substituting with substituents or lower substituents, or unsubstituted 5- to 9-membered ring heteroarylenes Yes. In some embodiments, the compound is used as described in the following Examples section, figures, or tables. It is a species of academic discipline.

[0058] The specific compounds provided herein contain asymmetric carbon atoms (optical or chiral centers) or it has a double bond, and from the perspective of absolute stereochemistry, the amino acid is (R)- or (S)- Enantiomers, racemates, diastereomers that can be defined as (D)- or (L). -, tautomers, geometric isomers, stereoisomer morphologies, and individual isomers are within the scope of this disclosure. It is contained within. The compounds provided herein are not suitable for synthesis and / or isolation. The compounds provided herein do not contain compounds that are known to be excessively concentrated in the art. The substances include compounds in racemic and optically pure forms. Optically active (R )- and (S)- or (D)- and (L)-isomers are chiral synthons or chiral synths. It may be prepared using reagents or decomposed using conventional techniques. If the listed compounds contain olefin bonds or other geometrically asymmetric centers, unless otherwise specified. The compound is intended to contain both E and Z geometric isomers.

[0059] As used herein, the term "isomer" means an isomer of the same number and type of atoms. These refer to compounds that have the same molecular weight but differ in terms of atomic structure or stereochemistry. vinegar.

[0060] As used herein, the term "tautomer" refers to a group of isomers that exist in equilibrium and have a certain isomer form. This refers to one of two or more structural isomers that can be easily converted from one isomer to another.

[0061] Certain compounds provided herein may exist in tautomer forms, and the compounds may exist in tautomer forms. It will be obvious to those skilled in the art that all such tautomer forms are within the scope of this disclosure. .

[0062] If the compounds disclosed herein have at least one chiral center, they are , as individual enantiomers and diastereomers, or such as racemates They can exist as a mixture of isomers. Separation of individual isomers or selective synthesis of individual isomers is possible. This is achieved by applying various methods well known to practitioners in the relevant technical field. Unless otherwise indicated. To the extent that all such isomers and mixtures thereof are not part of the compounds disclosed herein It is included within the scope of the object. Unless otherwise specified, the structures shown herein are of the same nature as the structure. Including all stereochemical forms, i.e., the (R) and (S) configurations of each asymmetric center. This is also intended. Therefore, a single stereochemistry that is generally recognized as stable by those skilled in the art. Isomers, as well as enantiomers and diastereomer mixtures of the compound, are within the scope of this disclosure. It is inside.

[0063] Unless otherwise stated, the structures shown herein also include one or more isotope-enriched atoms. It is also intended to contain compounds that differ only in their presence. For example, deuterium or Replacement of hydrogen with tritium, replacement of fluoride with 18F, or 13C or Except for carbon substitution with 14C-enriched carbon, compounds having this structure are within the scope of this disclosure. It is within the enclosure.

[0064] The compounds provided herein also include one or more of the atoms that make up such compounds. In this case, it may contain unnatural proportions of atomic isotopes. For example, the compound may contain trithio. Radioactive materials such as 3H, iodine-125 (125I), or carbon-14 (14C) They may be radiolabeled with an elemental isotope. All isotope variations of the compounds provided herein Motion, whether radioactive or not, is included in this disclosure.

[0065] Through this application, options, for example, each amino acid position containing more than one possible amino acid, Note that this is described in terms of Markush groups. Each member of a Markush group should be considered separately. This should be considered, and thereafter, including another embodiment, the Markush group is a single unit and It is especially intended that it should not be read in that way.

[0066] "Analog" or "analogue" is a term used by Chemis. Used according to its simple, ordinary meaning within try and biology, and another chemical It is structurally similar to the substance (i.e., the so-called "reference" compound), but its composition is different, for example, The substitution of one atom by an atom of a certain element, or in the presence of a specific functional group, or another Substitution of one functional group by another functional group, or absolute substitution of one or more chiral centers in a reference compound. Refers to compounds with different stereochemistry. Thus, an analog is a compound that is similar or equivalent in function and appearance to a reference compound but different in structure or origin. Points, but is a compound that is different in terms of structure or origin.

[0067] As used herein, the term "a" or "an" means one or more. In addition, as used herein, the phrase "substituted with a[n]" means that a particular Group can be substituted with one or more of any or all of the specified substituents. For example, if a group such as an alkyl group or a heteroaryl group is "substituted with unsubstituted C1-C20 Alkyl or unsubstituted 2-20 member heteroalkyl", the group can contain one or more Unsubstituted C1-C20 alkyl and / or one or more unsubstituted 2-20 member heteroalkyls.

[0068] Furthermore, if a moiety is substituted with an R substituent, the group can be referred to as "R-substituted". When a moiety ​​​​​​​​​​​​​​​​​This means that it can be replaced by one or more of the substitution genus. For example, Groups such as alkyl groups or heteroaryl groups are "unsubstituted C1-C20 alkyl or unsubstituted If it is "substituted with a 2-20 member heteroalkyl group", the group is one or more unsubstituted C1-C It may contain 20 alkyl and / or one or more unsubstituted 2-20 member heteroalkyl groups.

[0069] The descriptions of compounds provided herein are not limited by the principles of chemical bonding known to those skilled in the art. Therefore, if a group can be substituted with one or more substituents, Substitution follows the principles of chemical bonding and is not inherently unstable, as well as / ma Or it is unstable under ambient conditions such as aqueous, neutral, and some known physiological conditions. They are selected to yield compounds that are known to those skilled in the art to be highly likely to produce the desired result. For example, Heterocycloalkyl or heteroaryl compounds are bonded according to the principles of chemical bonding known to those skilled in the art. , bonded to the rest of the molecule via ring heteroatoms, thereby making the compound inherently unstable. The object is avoided.

[0070] The term "pharmaceutically acceptable salt" refers to a salt that preserves the biological efficacy and properties of a compound. They possess and are undesirable for use in other pharmaceuticals, either biologically or otherwise. This refers to salts that are not amino groups. In many cases, the compounds herein contain amino groups and / or carbo groups. The presence of xyl groups, or similar groups, can form acids and / or base salts. This is possible. Pharmaceutically acceptable acid addition salts can be formed using inorganic and organic acids. Inorganic acids that can be the source of salts include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. It contains. Organic acids that can be the source of salts include, for example, acetic acid, propionic acid, and glycol. Acids, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, que Mandelic acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-Tol This includes ensulfonic acid, salicylic acid, etc. Pharmaceutically acceptable base addition salts are inorganic salts. It can be formed using groups and organic bases. Inorganic bases that can be the source of the salt include, for example, na Thorium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, It contains copper, manganese, aluminum, etc., and is particularly preferably ammonium, potassium, These are sodium, calcium, and magnesium salts. These are organic bases from which salts can originate. This includes, for example, primary, secondary, and tertiary amines, as well as substituted amines, including naturally occurring substituted amines. Examples include cyclic amines, basic ion exchange resins, and more specifically, isopropylamine. Trimethylamine, diethylamine, triethylamine, tripropylamine, and It contains tanolamines, etc. Many of such salts were published on September 11, 1987. WO87 / 05297, Johnston et al. (The entire work is referenced in this book.) As described in the specification (which is incorporated into the specification), it is known in the art.

[0071] "To make contact" is used according to its obvious and ordinary meaning, and at least two Different species (e.g., chemical compounds, biomolecules, or cells) react, interact, and This refers to a process that allows for physical contact to occur. For example, contact This means that the compound is close enough for the cell to bind to the cell surface receptor. This includes a process that makes this possible.

[0072] As used herein, "contacting a cell" means that another compound or substance is in direct contact with the cell or in a state close enough to induce a desired biological effect within the cell.

[0073] As defined herein, terms such as "inhibit", "inhibiting", "inhibition" adversely affect (e.g., reduce) the activity or function as compared to the activity or function in the absence of the inhibitor. In embodiments, inhibition means adversely affecting (e.g., reducing) the concentration or level of a biomolecule such as a protein or mRNA as compared to the concentration or level of the biomolecule in the absence of the inhibitor. For example, inhibition includes reducing the level of mRNA expression in a cell. In embodiments, inhibition refers to a decrease in the activity of a specific biomolecule target, e.g., a protein target or an mRNA target. Thus, inhibition includes at least partially blocking, reducing, preventing, or delaying stimulation, or inactivating, desensitizing, or downregulating the signal transduction or enzyme activity or the amount of a biomolecule. In embodiments, inhibition refers to a decrease in the activity of a target biomolecule resulting from a direct interaction (e.g., the inhibitor binds to the target protein).

[0074] The term "inhibitor" also refers to detecting the expression or activity of a given gene or protein. This refers to a compound, composition, or substance that can be reduced. For example, an inhibitor is Compared to a control in the absence of the inhibitor, expression or activity was increased by 10%, 20%, and 30%. It can be reduced by 40%, 50%, 60%, 70%, 80%, 90%, or even more. Inhibitors include, for example, synthetic molecules or biological molecules such as oligonucleotides. .

[0075] As used herein, the terms “expression” and “gene expression” refer to mRNA expression and This refers to the steps involved in the translation of nucleic acids into proteins, including protein expression. , nucleic acids or proteins (e.g., PCR, ELISA, Southern blot, Southern blot) Western blotting, flow cytometry, FISH, immunofluorescence, immunofluorescence It can be detected using conventional techniques for detecting epidemiological histochemistry.

[0076] "Effective amount" refers to the amount of the compound that achieves a specified purpose compared to the absence of the compound (for example, the amount of the compound that does not achieve a specified purpose). Whether this achieves the intended effect, treats the disease, or reduces enzyme activity, To increase enzyme activity, decrease signaling pathways, or cause disease or condition A sufficient amount to alleviate one or more symptoms. The term "reduced activity" as used herein refers to a substance that reduces activity. "Amount to reduce enzyme activity" refers to the amount of enzyme needed to reduce enzyme activity compared to the absence of the antagonist. This refers to the amount of antagonist. As used herein, "amount that disrupts function" refers to the amount of antagonist. Antagonists are necessary to disrupt the function of an enzyme or protein compared to the absence of an antagonist. It refers to the quantity of "t".

[0077] As used herein, the term "in vivo" refers to a process that takes place within the body of the subject. It tastes good.

[0078] As used herein, the term “subject” refers to a human being selected for treatment or therapy. Alternatively, it can mean a non-human animal. In this embodiment, the subject is a human.

[0079] As used herein, the term “exvivo” refers to the odor of isolated tissue or cells. This refers to a process performed in vitro, where the tissue or cells processed are primary cells. It contains cells. Any culture medium used in this process, as is known in the art, It may be aqueous and non-toxic so as not to render tissues or cells unviable. Embodiments Therefore, the ex vivo process is performed in vitro using primary cells.

[0080] The term "administration" means providing a drug or composition to a medical professional. This includes administration by other means and self-administration.

[0081] The term "therapy" refers to the treatment of at least one indicator or disease or condition for improvement. This means the application of one or more specific procedures used. In embodiments, the specific procedures are 1 This involves the administration of one or more drugs.

[0082] The term “adjust” is used herein in its ordinary sense, as will be understood by those skilled in the art. It refers to the act of using something to change or alter one or more properties. In terms of the effect of regulatory factors on target molecules, the characteristics or functions of the target molecule, This involves adjusting the means to change the amount of the target molecule by increasing or decreasing it. This means that a disease modifier reduces the symptoms, causes, or characteristics of the target disease.

[0083] The term "nucleic acid" refers to a molecule consisting of at least two nucleotide monomers covalently bonded to each other. It refers to the compounds it contains. Nucleic acids include polynucleotides and double-stranded oligonucleotides. Oligonucleotides including single-stranded oligonucleotides, and their modified forms This includes the version.

[0084] The term "polynucleotide" refers to longer nucleic acids, e.g., 200, 300, 500, 1000, 2000, 3000, 5000, 7000, or 10,000 nuk It refers to the length of a rheotide. Non-exclusive examples of polynucleotides include genes and gene fragments. , exons, introns, intergenetic DNA (including, but not limited to, complex pigment DNA) (None), messenger RNA (mRNA), long non-coding RNA, transf ribosomal RNA, ribozyme, cDNA, recombinant polynucleotide, branched Polynucleotides, plasmids, vectors, isolated DNA sequences, and sequence isolation The RNA is included. Polynucleotides useful in the methods of this disclosure are natural nucleic acids. This may include sequences and their variants, artificial nucleic acid sequences, or combinations of such sequences.

[0085] The term "oligonucleotide" refers to a shorter nucleic acid, for example, 100 nucleos This refers to nucleic acids less than a centimeter in length. Oligonucleotides can be single-stranded or double-stranded. Oligonucleotides are naturally occurring ribonucleotides and naturally occurring deoxygenated oligonucleotides. Ribonucleotides, and / or naturally occurring ends, sugars, nucleic acid bases, and / or The nucleotide may contain one or more modifications to the internucleotide bonds. Non-exclusive examples of nucleotides include double-stranded oligonucleotides and single-stranded oligonucleotides. Tide, antisense oligonucleotides, small interfering RNA (siRNA), microR NA mimes, short hairpin RNA (shRNA), single-stranded small interfering RNA (ssR) NAi), RNaseH oligonucleotide, anti-microRNA oligonucleotide, standing Body-blocking oligonucleotides, exon-skipping oligonucleotides, CRI This includes SPR guide RNA and aptamers.

[0086] The term "double-stranded oligonucleotide" refers to an oligonucleotide that is essentially a double-stranded form. It means oti. Double-stranded oligonucleotides mimic siRNA or microRNA. Like an object, a biregion is formed between two antiparallel oligonucleotides that are not covalently bonded. The structure may include such a double-stranded oligonucleotide, which may have one or both of the double structures. Double-stranded oligonucleotides may have short nucleotide overhangs at one end. Furthermore, like shRNA, it possesses sufficient length and self-complementarity to form a double-stranded structure. It may contain a single oligonucleotide. Such a double-stranded oligonucleotide may be... It contains a Tem loop structure. Double-stranded nucleic acids have naturally occurring ends, sugars, nucleic acid bases, and / or may include one or more modifications to the phosphate group. Non-limiting double-stranded oligonucleotides. Typical examples include small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs). ), and microRNA mimes are included.

[0087] The terms "small interfering RNA" or "siRNA" refer to the RNA interference pathway. By promoting mRNA degradation before translation, gene expression is interfered with in a sequence-specific manner. This refers to a double-stranded oligonucleotide formed from separate antisense and sense strands. The antisense and sense strands of siRNA are not covalently bonded.

[0088] The term "microRNA mime" refers to a synthetic form of naturally occurring microRNA. It refers to a microRNA mime that contains one or more target mRNAs and complementary antisense strands. It includes an antisense strand and a complementary sense strand. In naturally occurring microRNAs, The sense strand is typically only partially complementary to its target mRNA, and the sense strand It is only partially complementary to the antisense strand. MicroRNA mimetics are naturally occurring. It may contain a nucleic acid base sequence that is 100% identical to the microRNA, or a natural Even if it contains nucleic acid base sequences that have less than 100% identity with the microRNA present. Good. For example, a microRNA mime is 100% complementary to the antisense strand. It may include chains.

[0089] The term "single-stranded RNA interference" or "ssRNAi" refers to the RNA interference pathway. By promoting mRNA degradation before translation, gene expression is interfered with in a sequence-specific manner. This refers to a single-stranded oligonucleotide.

[0090] The term "antisense strand" refers to a strand that is complementary to the target mRNA and is used in RNA-induced sirens. It is incorporated into the RISC complex and, via the RNA interference pathway, is sequence-specifically linked to gene sequencing. This refers to oligonucleotides of siRNA or ssRNAi that induce erasing. The antisense strand is sometimes called the "guide strand."

[0091] The term "sense strand" refers to the strand of a double-stranded oligonucleotide that is complementary to the antisense strand. This refers to liganucleotides. The sense strand is typically the antisense strand that is linked to the RISC-mediated structure. It is broken down after being absorbed. The sense chain is sometimes called the "passenger chain".

[0092] The term "dual region" refers to the nucleotide base pairing of a complementary oligonucleotide sequence. It refers to a structure formed by the formation of a double region, which is part of or complete a complementary arrangement. It can be formed from a complementary sequence of lengths.

[0093] The term "short hairpin RNA" or "shRNA" refers to RNA interference pathways. By promoting mRNA degradation before translation, gene expression is inhibited in a sequence-specific manner. Double-stranded oligonucleotides containing loop structures that are processed in cells by siRNA. It means Ochido.

[0094] The term "nucleotide overhang" refers to the overhang in double-stranded oligonucleotides. This refers to the adjacent single-stranded nucleotides at the end of a ligonucleotide.

[0095] The term "single-stranded oligonucleotide" refers to an oligonucleotide that does not hybridize to a complementary strand. It means nucleotide. Non-exclusive examples of single-stranded oligonucleotides include single-stranded small molecules. Interfering RNA (ssRNAi), RNaseH oligonucleotides (mediated by RNaseH) (OLIsognathic cells chemically modified to induce degradation of target RNA), anti-microwaves MicroRNA oligonucleotides (oligonucleotides complementary to microRNAs), stereobacteria Locking oligonucleotides (which interfere with the activity of target RNA without degrading it) exon skipping oligonucleotides (exon annular Oligonucleotides that hybridize with the ring portion to modify splicing), C This includes RISPR guide RNA and aptamers.

[0096] The term "hybridize" refers to the process of converting one nucleic acid into another based on the complementarity of their nucleic acid base sequences. This means annealing to nucleic acids. In the embodiment, the antisense strand is connected to the sense strand. It is hybridized. In one embodiment, the antisense strand is hybridized with the target mRNA sequence. Soybeans.

[0097] The term "complementary" refers to the ability to form pairs non-covalently via hydrogen bonds. It means nucleic acid bases.

[0098] The term "perfectly complementary" means that each nucleic acid base of the first nucleic acid is equivalent to each nucleic acid base of the second nucleic acid. This means that it is complementary to the target mRNA. In the embodiment, the antisense strand is complementary to its target mRNA. They are completely complementary. In the embodiment, the sense strand and anti strand of the double-stranded oligonucleotide. The sense strands are completely complementary along their entire length. In embodiments, double-stranded oligonucleotides are used. The sense and antisense strands of the nucleotide extend throughout the entire length of the double-stranded region of the siRNA. They are completely complementary, and one or both ends of either strand are single-stranded nucleotides. Includes.

[0099] The term "nucleoside" refers to nucleic acid bases and pentofuranosyl sugars (e.g., ribo). It refers to a monomer of either bisphosphonate or deoxyribose. Nucleoside is a nucleic acid salt. It may be modified with a group and / or sugar. In embodiments, the nucleoside is deoxyribonucle It is a rheoside. In the embodiment, the nucleoside is a ribonucleoside.

[0100] The term "nucleotide" refers to the covalent bond at the phosphate group of the 5' carbon of the pentafuranosyl sugar. It means a nucleoside. A nucleotide is a nucleic acid that consists of a base, sugar, or phosphate group. One or more of these can be modified. Nucleotides are linked directly or via linkers. It may have ligands. In the embodiment, the nucleotide is a deoxyribonucleotide. Yes. In the embodiment, the nucleotide is a ribonucleotide.

[0101] The term "nucleic acid base" refers to the heterocyclic base portion of a nucleoside or nucleotide. It tastes. Non-exclusive examples of nucleic acid bases include cytosine or its derivatives (e.g., cytosine a Nalog), guanine or its derivatives (e.g., guanine analogs), adenine or so Derivatives of (e.g., adenine analogs), thymine or its derivatives (e.g., thymine analogs) Log), uracil or its derivatives (e.g., uracil analogs), hypoxanthine or This includes its derivatives (for example, hypoxanthine analogs), xanthine or its derivatives (for example) For example, xanthine analogs, 7-methylguanine or its derivatives (e.g., 7-methyl Guanine analogs), deaza-adenine or its derivatives (e.g., deaza-adenine Nalog), deaza-guanine or its derivatives (e.g., deaza-guanine), deaza- Hypoxanthine or its derivatives, 5,6-dihydrouracil or its derivatives (for example) , 5,6-dihydrouracil analogs), 5-methylcytosine or its derivatives (e.g.) , 5-methylcytosine analogs), or 5-hydroxymethylcytosine or its derivatives The compound (e.g., a 5-hydroxymethylcytosine analog) is included. In the embodiment, Nucleic acid bases include adenine, guanine, hypoxanthine, xanthine, theobromine, and café. It is uric acid, or isoguanine, and may be substituted or modified in some cases. In the application form, nucleic acid bases are, [ka] It is and can be arbitrarily substituted or modified.

[0102] The term "modified nucleotide" refers to a naturally occurring nucleotide with one or more modified nucleotides. This refers to nucleotides that have modifications. Modifications are the nucleoside bonds between nucleotides. Modified nucleotides can be present in nucleic acid bases and / or sugar moieties. Modified nucleotides are, for example, enhanced. Cell uptake, enhanced affinity for other oligonucleotides or nucleic acid targets, Desirable benefits include increased stability in the presence of crease and / or reduced immune stimulation. Due to its properties, it may be preferred over the unmodified form. Modified nucleotides have a modified sugar moiety and Modified nucleotides may have both an unmodified sugar moiety and a modified phosphate group. Modified nucleotides may have a modified sugar moiety and an unmodified nucleic acid base. Rheotides may have modified sugar moieties and modified phosphate groups. Nucleic acids, polynucleotides, and Oligonucleotides may contain one or more modified nucleotides.

[0103] As used herein, the term “complement” refers to a complementary nucleotide or nucleo Nucleotides (e.g., RNA or DNA) that can base-pair with the sequence of a nucleotide or refers to a sequence of nucleotides. As described herein and generally known in the art As has been shown, the complementary (matching) nucleotide of adenosine is thymidine. The complementary (matching) nucleotide of guanidine is cytosine. Therefore, Complement is a group of nucleotides that base-pair with the corresponding complementary nucleotide of the second nucleic acid sequence. It may include a sequence. The complementary nucleotide is partially and also the nucleotide of the second nucleic acid sequence. They can be a perfect match. The complementary nucleotides can be perfectly identical to each nucleotide in the second nucleic acid sequence. If they match, the complement forms base pairs with each nucleotide in the second nucleic acid sequence. If the complement nucleotides partially match the nucleotides of the second nucleic acid sequence, then the complement Only a portion of the nucleotides forms base pairs with nucleotides in the second nucleic acid sequence. (Complementary sequence) Examples include coded arrays and non-coded arrays, where non-coded arrays are relative to coded arrays. It contains complementary nucleotides and therefore forms a complement of the coding sequence. Further examples are sense arrays and antisense arrays, where the sense array is the antisense array. It contains complementary nucleotides to the sequence, and therefore forms a complement to the antisense sequence. ru.

[0104] As described herein, when sequence complementarity is partial, only some nucleic acids are salt All nucleic acids match according to base pairing, or, if complete, match according to base pairing. Therefore, two complementary sequences are involved in the specific nucleotides involved in nucleic acid base pairing. It may have a certain proportion (i.e., about 60% complementarity across a particular region, preferably 6%). 5%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 9 (5%, 96%, 97%, 98%, 99%, or higher complementarity).

[0105] "Hybridization" is a process based on the well-understood principle of sequence complementarity, where one hybrid is created. This refers to the annealing of a main-stranded nucleic acid (such as a primer) to another nucleic acid. In one embodiment, the other nucleic acid is a single-stranded nucleic acid. Hybridization between nucleic acids The trend depends on the temperature and ionic strength of those environments, the length of nucleic acids, and the degree of complementarity. It exists. The effect of these parameters on hybridization is, for example, Sam Brook J, Fritsch EF, Maniatis T., Molecular cloning:a laboratory manual,Cold Spring Harbor Laboratory Press, New York (1989) It is described herein. When used herein, the primer or DNA elongation product hive Redylation can both form phosphodiester bonds. For the formation of phosphodiester bonds with available nucleotides or nucleotide analogs. Therefore, it is extendable.

[0106] The term "identical" or "identity rate" refers to two or more nucleic acid sequences or polypeptides. For sequences, use BLAST or BLA with the default parameters described below. When measured using the ST 2.0 sequence comparison algorithm, or manual alignment And by visual inspection (see, for example, the NCBI website), they are the same, or a specific proportion of amino acid residues or nucleotides that are the same (i.e., comparative win When compared and aligned for the maximum correspondence across a given area or region, Across a specific sequence, at least 60% identity, 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 any of the aforementioned values. Refers to two or more sequences or subsequences that have identity within the range defined by the two. This definition may also refer to or apply to the complement of the test sequence. The definition also This includes sequences with deletions and / or additions, as well as those with substitutions. (See below) Therefore, a preferred algorithm can explain gaps, insertions, and so on. Alignment for the purpose of determining sequence identity percentage is performed using methods such as BLAST and BL. AST-2, ALIGN, ALIGN-2, or Megalign (DNASTAR) Using publicly available computer software such as software, this technology This can be achieved in various ways within the scope of the field, across the entire length of the sequences being compared. Alignment measurement, including the algorithms necessary to achieve maximum alignment. Appropriate parameters for determining this can be determined by known methods.

[0107] compound In particular, it contains nucleic acids (A) covalently bonded to one or more half-life extension motifs (HLEMs). A compound is provided. For example, the compound has one half-life extension motif (HLEM), 2 One half-life extension motif (HLEM), three half-life extension motifs (HLEM), four Half-life extension motif (HLEM), or shared with five half-life extension motifs (HLEM). It contains bound nucleic acid (A).

[0108] In one embodiment, the compound has formula (I), (HLEM)zA (I), In the formula, z is an integer between 1 and 5.

[0109] In this embodiment, Z is 1. In this embodiment, Z is 2. In this embodiment, Z is , 3. In the embodiment, Z is 4. In the embodiment, Z is 5.

[0110] In one embodiment, nucleic acids covalently bind to one or more incorporation motifs (UMs). For example, Nucleic acids have one incorporation motif (UM), two incorporation motifs (UM), and three incorporation motifs. Incorporated motif (UM), four incorporated motifs (UM), or five incorporated motifs It forms a covalent bond with -f (UM).

[0111] In one embodiment, the compound has formula (II), (HLEM)zA-(UM)t (II), In the formula, t is an integer between 1 and 5.

[0112] In the embodiment, t is 1. In the embodiment, t is 2. In the embodiment, t is , 3. In the embodiment, t is 4. In the embodiment, t is 5.

[0113] In this embodiment, the half-life extension motif has the following structure [ka] k is an integer between 1 and 5.

[0114] L1 is independently a covalent linker. L2 is independently an unsubstituted alkylene. .

[0115] In the embodiment, k is 1. In the embodiment, k is 2. In the embodiment, k is , 3. In the embodiment, k is 4. In the embodiment, k is 5. Embodiment In this embodiment, k is an integer between 1 and 3.

[0116] In the embodiment, one or more L2 atoms may bond with one or more atoms of L1. One or more L2 atoms may bond with one or more atoms of L1, and one or more atoms may be the same or They may differ. In one embodiment, one or more L2 atoms bond to the same atom. In another embodiment, 1 One or more L2 atoms bond to different atoms. In this embodiment, one or more L2 atoms are the same or It bonds with different atoms.

[0117] In the embodiment, one or more L2s are independently L1A, L1B, L1C, L1D, or It can be coupled with L1E. In the embodiment, L2 can be independently coupled with L1A. In this embodiment, one L2 can be independently coupled to L1B. It can be coupled with L1C. In this embodiment, one L2 can independently be coupled with L1D. In this configuration, one L2 can independently be coupled with L1E.

[0118] In this embodiment, L1A, L1B, L1C, L1D, and L1E are independent, combined, - N(R20)-, -O-, -S-, -C(O)-, -N(R20)C(O)-, -C(O )N(R21)-, -N(R20)C(O)N(R21)-, -C(O)O-, -OC( O)-, -N(R20)C(O)O-, -OC(O)N(R21)-, -OPO2-O- , -OP(O)(S)-O-, -OP(O)(R22)-O-, -OP(S)(R 22)-O-, -OP(O)(NR20R21)-N-, -OP(S)(NR20R 21)-N-, -OP(O)(NR20R21)-O-, -OP(S)(NR20R 21)-O-, -P(O)(NR20R21)-N-, -P(S)(NR20R21)- N-, -P(O)(NR20R21)-O-, -P(S)(NR20R21)-O-, - SS-, substituted or unsubstituted alkylenes, substituted or unsubstituted heteroalkylenes, substituted Alternatively, unsubstituted cycloalkylenes, substituted or unsubstituted heterocycloalkylenes, and substituted ones as well. Alternatively, it may be an unsubstituted arylene, or a substituted or unsubstituted heteroarylene. Each R20 R21 and R22 are independently hydrogen or unsubstituted C1-C10 alkyl groups.

[0119] In the embodiment, one or more L2s are independently L1A, L1B, L1C, L1D, or It can be coupled with L1E. In the embodiment, one or more L2s can be independently coupled with L1A. In the embodiment, one or more L2s can be independently coupled to L1B. The above L2 can independently be coupled with L1C. In the embodiment, one or more L2s can independently It can be coupled with L1D. In the embodiment, one or more L2s can be independently coupled with L1E.

[0120] In the embodiment, at least one L2 can be independently coupled to L1A. At least one L2 can be independently coupled with L1B. In the embodiment, at least 1 Each L2 can independently couple with L1C. In this embodiment, at least one L2 is independent And it can be coupled with L1D. In the embodiment, at least one L2 is independently coupled with L1E and They can combine.

[0121] In the embodiment, one L2 can be independently coupled with L1A. In the embodiment, one L L2 can independently be coupled with L1B. In this embodiment, one L2 can independently be coupled with L1C. They can be coupled. In the embodiment, one L2 can be independently coupled with L1D. In the embodiment, One L2 can independently connect to L1E.

[0122] In this embodiment, L1A is a bond, -N(R20)-, -O-, -S-, -C(O)-, -N(R20)C(O)-, -C(O)N(R21)-, -N(R20)C(O)N(R 21)-, -C(O)O-, -OC(O)-, -N(R20)C(O)O-, -OC(O )N(R21)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)( R22)-O-, -OP(S)(R22)-O-, -OP(O)(NR20R21) -N-, -OP(S)(NR20R21)-N-, -OP(O)(NR20R21) -O-, -OP(S)(NR20R21)-O-, -P(O)(NR20R21)-N -, -P(S)(NR20R21)-N-, -P(O)(NR20R21)-O-, -P (S)(NR20R21)-O-, -SS-, substituted or unsubstituted alkylene, also substituted. or unsubstituted heteroalkylenes, substituted or unsubstituted cycloalkylenes, substituted or unsubstituted cycloalkylenes Substituted heterocycloalkylenes, substituted or unsubstituted arylenes, or substituted or unsubstituted arylenes. It is a heteroarylene.

[0123] In the embodiment, L1A is a coupling. In the embodiment, L1A is -N(R20)- Yes. In the embodiment, L1A is -O- or -S-. In the embodiment, L1A is -C(O)-. In the embodiment, L1A is -N(R20)C(O)- or -C( O)N(R21)-. In this embodiment, L1A is -N(R20)C(O)N(R2 1) -. In this embodiment, L1A is -C(O)O- or -OC(O)-. In this embodiment, L1A is -N(R20)C(O)O- or -OC(O)N(R21) -In this embodiment, L1A is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R22)-O-, -OP(O)(NR20R21)-N-, or O -P(O)(NR20R21)-O-. In the embodiment, L1A is -P(O)(N R20R21)-N-, -P(S)(NR20R21)-N-, -P(O)(NR20R 21)-O-, or -P(S)(NR20R21)-O-. In the embodiment, L1 A is -SS-.

[0124] In the embodiment, L1A is independently a substituted or unsubstituted alkylene (e.g., C1-C2 (0, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1A is independently a substituted alkylene (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1A is independent of unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C 8, C1-C6, C1-C4, or C1-C2). In this embodiment, L1A is independent The C1-C20 alkylene is either substituted or unsubstituted. In the embodiment, L1A is independently And it is a substituted C1-C20 alkylene. In the embodiment, L1A is independently an unsubstituted C1 -C20 alkylene. In the embodiment, L1A is independently substituted or unsubstituted C1- It is a C12 alkylene. In the embodiment, L1A is independently a substituted C1-C12 alkylene. In this embodiment, L1A is independently an unsubstituted C1-C12 alkylene. In the application form, L1A is independently a substituted or unsubstituted C1-C8 alkylene. In this embodiment, L1A is independently a substituted C1-C8 alkylene. In this embodiment, L1A is Independently, it is an unsubstituted C1-C8 alkylene. In the embodiment, L1A is independently substituted Or it is an unsubstituted C1-C6 alkylene. In the embodiment, L1A is independently a substituted C1 -C6 alkylene. In the embodiment, L1A is independently an unsubstituted C1-C6 alkylene. In this embodiment, L1A is independently a substituted or unsubstituted C1-C4 alkylene. Yes. In the embodiment, L1A is independently a substituted C1-C4 alkylene. In this embodiment, L1A is independently an unsubstituted C1-C4 alkylene. In this embodiment, L1A is independently substituted or unsubstituted ethylene. It is ethylene. In the embodiment, L1A is independently unsubstituted ethylene. In the embodiment, L1A is independently a substituted or unsubstituted methylene group. In the embodiment, L1A is independently , is a substituted methylene group. In this embodiment, L1A is independently an unsubstituted methylene group.

[0125] In the embodiment, L1A is independently a substituted or unsubstituted heteroalkylene (e.g., 2- (20 people, 2-12 people, 2-8 people, 2-6 people, 4-6 people, 2-3 people, or 4-5 people) In the embodiment, L1A is independently a substituted heteroalkylene (e.g., 2-20 members, 2 (~12 members, 2~8 members, 2~6 members, 4~6 members, 2~3 members, or 4~5 members). Implementation form In this state, L1A independently forms unsubstituted heteroalkylenes (e.g., 2-20 member, 2-12 member). (2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members). In the embodiment, L1A is independently a substituted or unsubstituted 2- to 20-membered heteroalkylene. In the embodiment, L1A is independently a substituted 2- to 20-membered heteroalkylene. In the embodiment, L1A is Independently, they are unsubstituted 2-20 member heteroalkylenes. In the embodiment, L1A is independently , substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L1A is independently , substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1A is independently unsubstituted 2- It is an 8-membered heteroalkylene. In the embodiment, L1A is independently substituted or unsubstituted 2~ It is a 6-membered heteroalkylene. In the embodiment, L1A is independently a substituted 2- to 6-membered heteroalkylene. It is a lukilen. In the embodiment, L1A is independently an unsubstituted 2-6 member heteroalkylene. In some embodiments, L1A is independently a substituted or unsubstituted 4-6 member heteroalkylene. Yes. In the embodiment, L1A is independently a substituted 4-6 member heteroalkylene. In this state, L1A is independently an unsubstituted 4-6 member heteroalkylene. In the embodiment, L 1A is independently a substituted or unsubstituted 2-3 member heteroalkylene. In the embodiment, L 1A is independently a substituted 2-3 member heteroalkylene. In the embodiment, L1A is independently It is an unsubstituted 2-3 member heteroalkylene. In the embodiment, L1A is independently substituted or are unsubstituted 4-5 member heteroalkylenes. In the embodiment, L1A is independently a substituted 4 It is a ~5-membered heteroalkylene. In the embodiment, L1A is independently an unsubstituted 4-5 membered heteroalkylene. It is roalkylene.

[0126] In this embodiment, L1B is a bond, -N(R20)-, -O-, -S-, -C(O)-, -N(R20)C(O)-, -C(O)N(R21)-, -N(R20)C(O)N(R 21)-, -C(O)O-, -OC(O)-, -N(R20)C(O)O-, -OC(O )N(R21)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)( R22)-O-, -OP(S)(R22)-O-, -OP(O)(NR20R21) -N-, -OP(S)(NR20R21)-N-, -OP(O)(NR20R21) -O-, -OP(S)(NR20R21)-O-, -P(O)(NR20R21)-N -, -P(S)(NR20R21)-N-, -P(O)(NR20R21)-O-, -P (S)(NR20R21)-O-, -SS-, substituted or unsubstituted alkylene, also substituted. or unsubstituted heteroalkylenes, substituted or unsubstituted cycloalkylenes, substituted or unsubstituted cycloalkylenes Substituted heterocycloalkylenes, substituted or unsubstituted arylenes, or substituted or unsubstituted arylenes. It is a heteroarylene.

[0127] In the embodiment, L1B is a bond. In the embodiment, L1B is -N(R20)- Yes. In the embodiment, L1B is -O- or -S-. In the embodiment, L1B is -C(O)-. In the embodiment, L1B is -N(R20)C(O)- or -C( O)N(R21)-. In this embodiment, L1B is -N(R20)C(O)N(R2 1) -. In the embodiment, L1B is -C(O)O- or -OC(O)-. In this embodiment, L1B is -N(R20)C(O)O- or -OC(O)N(R21) -In this embodiment, L1B is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R22)-O-, -OP(O)(NR20R21)-N-, or O -P(O)(NR20R21)-O-. In the embodiment, L1B is -P(O)(N R20R21)-N-, -P(S)(NR20R21)-N-, -P(O)(NR20R 21)-O-, or -P(S)(NR20R21)-O-. In the embodiment, L1 B is -SS-.

[0128] In the embodiment, L1B is independently a substituted or unsubstituted alkylene (e.g., C1-C2 (0, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1B is independently a substituted alkylene (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1B is independent of unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C 8, C1-C6, C1-C4, or C1-C2). In this embodiment, L1B is independent The C1-C20 alkylene is either substituted or unsubstituted. In the embodiment, L1B is independently And it is a substituted C1-C20 alkylene. In the embodiment, L1B is independently an unsubstituted C1 -C20 alkylene. In the embodiment, L1B is independently substituted or unsubstituted C1- It is a C12 alkylene. In the embodiment, L1B is independently a substituted C1-C12 alkylene. In this embodiment, L1B is independently an unsubstituted C1-C12 alkylene. In the application form, L1B is independently a substituted or unsubstituted C1-C8 alkylene. In this embodiment, L1B is independently a substituted C1-C8 alkylene. In this embodiment, L1B is Independently, it is an unsubstituted C1-C8 alkylene. In the embodiment, L1B is independently substituted or unsubstituted C1-C6 alkylene. In the embodiment, L1B is independently substituted C1 -C6 alkylene. In the embodiment, L1B is independently an unsubstituted C1-C6 alkylene. In this embodiment, L1B is independently a substituted or unsubstituted C1-C4 alkylene. Yes. In the embodiment, L1B is independently a substituted C1-C4 alkylene. In this embodiment, L1B is independently an unsubstituted C1-C4 alkylene. In this embodiment, L1B is either substituted or unsubstituted ethylene. It is ethylene. In the embodiment, L1B is independently unsubstituted ethylene. In the embodiment, L1B is independently a substituted or unsubstituted methylene group. In the embodiment, L1B is independently , is a substituted methylene group. In the embodiment, L1B is independently an unsubstituted methylene group.

[0129] In the embodiment, L1B is independently a substituted or unsubstituted heteroalkylene (e.g., 2~ (20 people, 2-12 people, 2-8 people, 2-6 people, 4-6 people, 2-3 people, or 4-5 people) In the embodiment, L1B is independently a substituted heteroalkylene (e.g., 2-20 members, 2 (~12 members, 2~8 members, 2~6 members, 4~6 members, 2~3 members, or 4~5 members). Implementation form In this state, L1B independently forms unsubstituted heteroalkylenes (e.g., 2-20 member, 2-12 member). (2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members). In the embodiment, L1B is independently a substituted or unsubstituted 2- to 20-membered heteroalkylene. In the embodiment, L1B is independently a substituted 2- to 20-membered heteroalkylene. In the embodiment, L1B is Independently, they are unsubstituted 2-20 member heteroalkylenes. In the embodiment, L1B is independently , substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L1B is independently , substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1B is independently an unsubstituted 2- It is an 8-membered heteroalkylene. In the embodiment, L1B is independently substituted or unsubstituted 2~ It is a 6-membered heteroalkylene. In the embodiment, L1B is independently a substituted 2- to 6-membered heteroalkylene. It is a lukilen. In the embodiment, L1B is independently an unsubstituted 2- to 6-membered heteroalkylene. Yes. In the embodiment, L1B is independently a substituted or unsubstituted 4-6 member heteroalkylene. Yes. In the embodiment, L1B is independently a substituted 4-6 member heteroalkylene. In this state, L1B is independently an unsubstituted 4-6 member heteroalkylene. In the embodiment, L 1B is independently a substituted or unsubstituted 2-3 member heteroalkylene. In the embodiment, L 1B is independently a substituted 2-3 member heteroalkylene. In the embodiment, L1B is independently It is an unsubstituted 2-3 member heteroalkylene. In the embodiment, L1B is independently substituted or are unsubstituted 4-5 member heteroalkylenes. In the embodiment, L1B is independently a substituted 4 It is a ~5-membered heteroalkylene. In the embodiment, L1B is independently an unsubstituted 4-5 membered heteroalkylene. It is roalkylene.

[0130] In this embodiment, L1C is a bond, -N(R2O)-, -O-, -S-, -C(O)-, -N(R20)C(O)-, -C(O)N(R21)-, -N(R20)C(O)N(R 21)-, -C(O)O-, -OC(O)-, -N(R20)C(O)O-, -OC(O )N(R21)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)( R22)-O-, -OP(S)(R22)-O-, -OP(O)(NR20R21) -N-, -OP(S)(NR20R21)-N-, -OP(O)(NR20R21) -O-, -OP(S)(NR20R21)-O-, -P(O)(NR20R21)-N -, -P(S)(NR20R21)-N-, -P(O)(NR20R21)-O-, -P (S)(NR20R21)-O-, -SS-, substituted or unsubstituted alkylene, also substituted. or unsubstituted heteroalkylenes, substituted or unsubstituted cycloalkylenes, substituted or unsubstituted cycloalkylenes Substituted heterocycloalkylenes, substituted or unsubstituted arylenes, or substituted or unsubstituted arylenes. It is a heteroarylene.

[0131] In the embodiment, L1C is a bond. In the embodiment, L1C is -N(R20)- Yes. In the embodiment, L1C is -O- or -S-. In the embodiment, L1C is -C(O)-. In the embodiment, L1C is -N(R20)C(O)- or -C( O)N(R21)-. In this embodiment, L1C is -N(R20)C(O)N(R2 1) -. In the embodiment, L1C is -C(O)O- or -OC(O)-. In this embodiment, L1C is -N(R20)C(O)O- or -OC(O)N(R21) -In this embodiment, L1C is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R22)-O-, -OP(O)(NR20R21)-N-, or O -P(O)(NR20R21)-O-. In the embodiment, L1C is -P(O)(N R20R21)-N-, -P(S)(NR20R21)-N-, -P(O)(NR20R 21)-O-, or -P(S)(NR20R21)-O-. In the embodiment, L1 C is -SS-.

[0132] In the embodiment, L1C is independently a substituted or unsubstituted alkylene (e.g., C1-C2 (0, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1C is independently a substituted alkylene (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1C is independently an unsubstituted alkylene (e.g., C1-C20, C1-C12, C1-C 8, C1-C6, C1-C4, or C1-C2). In this embodiment, L1C is independent The C1-C20 alkylene is either substituted or unsubstituted. In the embodiment, L1C is independently And it is a substituted C1-C20 alkylene. In the embodiment, L1C is independently an unsubstituted C1 -C20 alkylene. In the embodiment, L1C is independently substituted or unsubstituted C1- It is a C12 alkylene. In the embodiment, L1C is independently a substituted C1-C12 alkylene. In this embodiment, L1C is independently an unsubstituted C1-C12 alkylene. In the application form, L1C is independently a substituted or unsubstituted C1-C8 alkylene. In this embodiment, L1C is independently a substituted C1-C8 alkylene. In this embodiment, L1C is Independently, it is an unsubstituted C1-C8 alkylene. In the embodiment, L1C is independently substituted. or unsubstituted C1-C6 alkylene. In the embodiment, L1C is independently substituted C1 -C6 alkylene. In the embodiment, L1C is independently an unsubstituted C1-C6 alkylene. In this embodiment, L1C is independently a substituted or unsubstituted C1-C4 alkylene. Yes. In the embodiment, L1C is independently a substituted C1-C4 alkylene. In this embodiment, L1C is independently an unsubstituted C1-C4 alkylene. In this embodiment, L1C is either substituted or unsubstituted ethylene. It is ethylene. In the embodiment, L1C is independently unsubstituted ethylene. In the embodiment, L1C is independently a substituted or unsubstituted methylene group. In the embodiment, L1C is independently , is a substituted methylene group. In this embodiment, L1C is independently an unsubstituted methylene group.

[0133] In the embodiment, L1C is independently a substituted or unsubstituted heteroalkylene (e.g., 2- (20 people, 2-12 people, 2-8 people, 2-6 people, 4-6 people, 2-3 people, or 4-5 people) In the embodiment, L1C is independently a substituted heteroalkylene (e.g., 2-20 members, 2 (~12 members, 2~8 members, 2~6 members, 4~6 members, 2~3 members, or 4~5 members). Implementation form In this state, L1C independently forms unsubstituted heteroalkylenes (e.g., 2-20 member, 2-12 member). (2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members). In the embodiment, L1C is independently a substituted or unsubstituted 2- to 20-membered heteroalkylene. In the embodiment, L1C is independently a substituted 2- to 20-membered heteroalkylene. In the embodiment, L1C is Independently, they are unsubstituted 2-20 member heteroalkylenes. In the embodiment, L1C is independently , substituted or unsubstituted 2-8 member heteroalkylenes. In the embodiment, L1C is independently , substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1C is independently unsubstituted 2- It is an 8-membered heteroalkylene. In the embodiment, L1C is independently substituted or unsubstituted 2~ It is a 6-membered heteroalkylene. In the embodiment, L1C is independently a substituted 2- to 6-membered heteroalkylene. It is a lukilen. In the embodiment, L1C is independently an unsubstituted 2-6 member heteroalkylene. Yes. In the embodiment, L1C is independently a substituted or unsubstituted 4-6 member heteroalkylene. Yes. In the embodiment, L1C is independently a substituted 4-6 member heteroalkylene. In this state, L1C is independently an unsubstituted 4-6 member heteroalkylene. In the embodiment, L 1C is independently a substituted or unsubstituted 2-3 member heteroalkylene. In the embodiment, L 1C is independently a substituted 2-3 member heteroalkylene. In the embodiment, L1C is independently It is an unsubstituted 2-3 member heteroalkylene. In the embodiment, L1C is independently substituted. or are unsubstituted 4-5 member heteroalkylenes. In the embodiment, L1C is independently a substituted 4 It is a ~5-membered heteroalkylene. In the embodiment, L1C is independently an unsubstituted 4-5 membered heteroalkylene. It is roalkylene.

[0134] In this embodiment, L1D is a bond, -N(R2O)-, -O-, -S-, -C(O)-, -N(R20)C(O)-, -C(O)N(R21)-, -N(R20)C(O)N(R 21)-, -C(O)O-, -OC(O)-, -N(R20)C(O)O-, -OC(O )N(R21)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)( R22)-O-, -OP(S)(R22)-O-, -OP(O)(NR20R21) -N-, -OP(S)(NR20R21)-N-, -OP(O)(NR20R21) -O-, -OP(S)(NR20R21)-O-, -P(O)(NR20R21)-N -, -P(S)(NR20R21)-N-, -P(O)(NR20R21)-O-, -P (S)(NR20R21)-O-, -SS-, substituted or unsubstituted alkylene, also substituted. or unsubstituted heteroalkylenes, substituted or unsubstituted cycloalkylenes, substituted or unsubstituted cycloalkylenes Substituted heterocycloalkylenes, substituted or unsubstituted arylenes, or substituted or unsubstituted arylenes. It is a heteroarylene.

[0135] In the embodiment, L1D is a coupling. In the embodiment, L1D is -N(R20)- Yes. In the embodiment, L1D is -O- or -S-. In the embodiment, L1D is -C(O)-. In the embodiment, L1D is -N(R20)C(O)- or -C( O)N(R21)-. In this embodiment, L1D is -N(R20)C(O)N(R2 1) -. In the embodiment, L1D is -C(O)O- or -OC(O)-. In this embodiment, L1D is -N(R20)C(O)O- or -OC(O)N(R21) -In this embodiment, L1D is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R22)-O-, -OP(O)(NR20R21)-N-, or O -P(O)(NR20R21)-O-. In the embodiment, L1D is -P(O)(N R20R21)-N-, -P(S)(NR20R21)-N-, -P(O)(NR20R 21)-O-, or -P(S)(NR20R21)-O-. In the embodiment, L1 D is -SS-.

[0136] In the embodiment, L1D is independently a substituted or unsubstituted alkylene (e.g., C1-C2 (0, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1D is independently a substituted alkylene (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1D is independent of unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C 8, C1-C6, C1-C4, or C1-C2). In this embodiment, L1D is independent The C1-C20 alkylene is either substituted or unsubstituted. In the embodiment, L1D is independently And it is a substituted C1-C20 alkylene. In the embodiment, L1D is independently an unsubstituted C1 -C20 alkylene. In the embodiment, L1D is independently substituted or unsubstituted C1- It is a C12 alkylene. In the embodiment, L1D is independently a substituted C1-C12 alkylene. In this embodiment, L1D is independently an unsubstituted C1-C12 alkylene. In the implementation form, L1D is independently a substituted or unsubstituted C1-C8 alkylene. In this embodiment, L1D is independently a substituted C1-C8 alkylene. In this embodiment, L1D is Independently, it is an unsubstituted C1-C8 alkylene. In the embodiment, L1D is independently substituted or unsubstituted C1-C6 alkylene. In the embodiment, L1D is independently substituted C1 -C6 alkylene. In the embodiment, L1D is independently an unsubstituted C1-C6 alkylene. In this embodiment, L1D is independently a substituted or unsubstituted C1-C4 alkylene. Yes. In the embodiment, L1D is independently a substituted C1-C4 alkylene. In this embodiment, L1D is independently an unsubstituted C1-C4 alkylene. In this embodiment, L1D is independently substituted or unsubstituted ethylene. It is ethylene. In the embodiment, L1D is independently unsubstituted ethylene. In the embodiment, L1D is independently a substituted or unsubstituted methylene group. In the embodiment, L1D is independently , is a substituted methylene group. In the embodiment, L1D is independently an unsubstituted methylene group.

[0137] In the embodiment, L1D is independently a substituted or unsubstituted heteroalkylene (e.g., 2- (20 people, 2-12 people, 2-8 people, 2-6 people, 4-6 people, 2-3 people, or 4-5 people) In the embodiment, L1D is independently a substituted heteroalkylene (e.g., 2-20 members, 2 (~12 members, 2~8 members, 2~6 members, 4~6 members, 2~3 members, or 4~5 members). Implementation form In this state, L1D independently forms unsubstituted heteroalkylenes (e.g., 2-20 member, 2-12 member). (2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members). In the embodiment, L1D is independently a substituted or unsubstituted 2- to 20-membered heteroalkylene. In embodiments, L1D is independently a substituted 2- to 20-membered heteroalkylene. In the embodiment, L1D is Independently, they are unsubstituted 2-20 member heteroalkylenes. In the embodiment, L1D is independently , substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L1D is independently , substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1D is independently an unsubstituted 2- It is an 8-membered heteroalkylene. In the embodiment, L1D is independently substituted or unsubstituted 2~ It is a 6-membered heteroalkylene. In the embodiment, L1D is independently a substituted 2- to 6-membered heteroalkylene. It is a lukilen. In the embodiment, L1D is independently an unsubstituted 2-6 member heteroalkylene. Yes. In the embodiment, L1D is independently a substituted or unsubstituted 4-6 member heteroalkylene. Yes. In the embodiment, L1D is independently a substituted 4- to 6-membered heteroalkylene. In this state, L1D is independently an unsubstituted 4-6 member heteroalkylene. In the embodiment, L 1D is independently a substituted or unsubstituted 2-3 member heteroalkylene. In the embodiment, L 1D is independently a substituted 2-3 member heteroalkylene. In the embodiment, L1D is independently It is an unsubstituted 2-3 member heteroalkylene. In the embodiment, L1D is independently substituted or are unsubstituted 4-5 member heteroalkylenes. In the embodiment, L1D is independently a substituted 4 It is a ~5-membered heteroalkylene. In the embodiment, L1D is independently an unsubstituted 4-5 membered heteroalkylene. It is roalkylene.

[0138] In this embodiment, L1E is a bond, -N(R20)-, -O-, -S-, -C(O)-, -N(R20)C(O)-, -C(O)N(R21)-, -N(R20)C(O)N(R 21)-, -C(O)O-, -OC(O)-, -N(R20)C(O)O-, -OC(O )N(R21)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)( R22)-O-, -OP(S)(R22)-O-, -OP(O)(NR20R21) -N-, -OP(S)(NR20R21)-N-, -OP(O)(NR20R21) -O-, -OP(S)(NR20R21)-O-, -P(O)(NR20R21)-N -, -P(S)(NR20R21)-N-, -P(O)(NR20R21)-O-, -P (S)(NR20R21)-O-, -SS-, substituted or unsubstituted alkylene, also substituted. or unsubstituted heteroalkylenes, substituted or unsubstituted cycloalkylenes, substituted or unsubstituted cycloalkylenes Substituted heterocycloalkylenes, substituted or unsubstituted arylenes, or substituted or unsubstituted arylenes. It is a heteroarylene.

[0139] In the embodiment, L1E is a coupling. In the embodiment, L1E is -N(R20)- Yes. In the embodiment, L1E is -O- or -S-. In the embodiment, L1E is -C(O)-. In the embodiment, L1E is -N(R20)C(O)- or -C( O)N(R21)-. In this embodiment, L1E is -N(R20)C(O)N(R2 1) -. In the embodiment, L1E is -C(O)O- or -OC(O)-. In this embodiment, L1E is -N(R20)C(O)O- or -OC(O)N(R21) -In this embodiment, L1E is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R22)-O-, -OP(O)(NR20R21)-N-, or O -P(O)(NR20R21)-O-. In the embodiment, L1E is -P(O)(N R20R21)-N-, -P(S)(NR20R21)-N-, -P(O)(NR20R 21)-O-, or -P(S)(NR20R21)-O-. In the embodiment, L1 E is -SS-.

[0140] In the embodiment, L1E is independently a substituted or unsubstituted alkylene (e.g., C1-C2 (0, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1E is independently a substituted alkylene (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L1E is independent of unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C 8, C1-C6, C1-C4, or C1-C2). In this embodiment, L1E is independent The C1-C20 alkylene is either substituted or unsubstituted. In the embodiment, L1E is independently And it is a substituted C1-C20 alkylene. In the embodiment, L1E is independently an unsubstituted C1 -C20 alkylene. In the embodiment, L1E is independently substituted or unsubstituted C1- It is a C12 alkylene. In the embodiment, L1E is independently a substituted C1-C12 alkylene. In this embodiment, L1E is independently an unsubstituted C1-C12 alkylene. In the application form, L1E is independently a substituted or unsubstituted C1-C8 alkylene. In this embodiment, L1E is independently a substituted C1-C8 alkylene. In this embodiment, L1E is Independently, it is an unsubstituted C1-C8 alkylene. In the embodiment, L1E is independently substituted or unsubstituted C1-C6 alkylene. In the embodiment, L1E is independently substituted C1 -C6 alkylene. In the embodiment, L1E is independently an unsubstituted C1-C6 alkylene. In this embodiment, L1E is independently a substituted or unsubstituted C1-C4 alkylene. Yes. In the embodiment, L1E is independently a substituted C1-C4 alkylene. In this embodiment, L1E is independently an unsubstituted C1-C4 alkylene. In this embodiment, L1E is independently substituted or unsubstituted ethylene. It is ethylene. In the embodiment, L1E is independently unsubstituted ethylene. In the embodiment, L1E is independently a substituted or unsubstituted methylene group. In the embodiment, L1E is independently , is a substituted methylene group. In the embodiment, L1E is independently an unsubstituted methylene group.

[0141] In the embodiment, L1E is independently a substituted or unsubstituted heteroalkylene (e.g., 2- (20 people, 2-12 people, 2-8 people, 2-6 people, 4-6 people, 2-3 people, or 4-5 people) In the embodiment, L1E is independently a substituted heteroalkylene (e.g., 2-20 members, 2 (~12 members, 2~8 members, 2~6 members, 4~6 members, 2~3 members, or 4~5 members). Implementation form In this state, L1E independently forms unsubstituted heteroalkylenes (e.g., 2-20 member, 2-12 member). (2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members). In the embodiment, L1E is independently a substituted or unsubstituted 2- to 20-membered heteroalkylene. In the embodiment, L1E is independently a substituted 2- to 20-membered heteroalkylene. In the embodiment, L1E is Independently, they are unsubstituted 2-20 member heteroalkylenes. In the embodiment, L1E is independently , substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L1E is independently , substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1E is independently an unsubstituted 2- It is an 8-membered heteroalkylene. In the embodiment, L1E is independently substituted or unsubstituted 2~ It is a 6-membered heteroalkylene. In the embodiment, L1E is independently a substituted 2- to 6-membered heteroalkylene. It is a lukilen. In the embodiment, L1E is independently an unsubstituted 2-6 member heteroalkylene. Yes. In the embodiment, L1E is independently a substituted or unsubstituted 4-6 member heteroalkylene. Yes. In the embodiment, L1E is independently a substituted 4- to 6-membered heteroalkylene. In this state, L1E is independently an unsubstituted 4-6 member heteroalkylene. In the embodiment, L 1E is independently a substituted or unsubstituted 2-3 member heteroalkylene. In the embodiment, L 1E is independently a substituted 2-3 member heteroalkylene. In the embodiment, L1E is independently It is an unsubstituted 2-3 member heteroalkylene. In the embodiment, L1E is independently substituted or are unsubstituted 4-5 member heteroalkylenes. In the embodiment, L1E is independently a substituted 4 It is a ~5-membered heteroalkylene. In the embodiment, L1E is independently an unsubstituted 4-5 membered heteroalkylene. It is roalkylene.

[0142] In this embodiment, each of R20, R21, and R22 is independently hydrogen or unsubstituted C1 -It is a C10 alkyl group.

[0143] In the embodiment, R20 is independently hydrogen or an unsubstituted C1-C10 alkyl group. In the embodiment, R20 is independently hydrogen. In the embodiment, R20 is unsubstituted C1-C1 It is alkyl. In the embodiment, R20 is an unsubstituted C1-C8 alkyl. In this embodiment, R20 is an unsubstituted C1-C6 alkyl group. In this embodiment, R20 is unsubstituted. It is a C1-C5 alkyl group. In the embodiment, R20 is an unsubstituted C1-C4 alkyl group. In the embodiment, R20 is an unsubstituted C1-C3 alkyl. In the embodiment, R20 is , is unsubstituted methyl. In the embodiment, R20 is unsubstituted ethyl. In the embodiment, R20 is unsubstituted propyl. In the embodiment, R20 is unsubstituted isopropyl. In the embodiment, R20 is unsubstituted n-butyl. It is t-butyl. In the embodiment, R20 is unsubstituted 2-butyl. In the embodiment, R20 is unsubstituted isobutyl.

[0144] In the embodiment, R21 is independently hydrogen or an unsubstituted C1-C10 alkyl group. In the embodiment, R21 is independently hydrogen. In the embodiment, R21 is unsubstituted C1-C It is 10 alkyl. In the embodiment, R21 is an unsubstituted C1-C8 alkyl. In the embodiment, R21 is an unsubstituted C1-C6 alkyl. It is a substituted C1-C5 alkyl. In the embodiment, R21 is an unsubstituted C1-C4 alkyl. In the embodiment, R21 is an unsubstituted C1-C3 alkyl. R21 is an unsubstituted methyl group. In the embodiment, R21 is an unsubstituted ethyl group. In the embodiment, In this embodiment, R21 is unsubstituted propyl. In the embodiment, R21 is unsubstituted n-butyl. It is substituted t-butyl. In the embodiment, R21 is unsubstituted 2-butyl. In the embodiment R21 is unsubstituted isobutyl.

[0145] In the embodiment, R22 is independently hydrogen or an unsubstituted C1-C10 alkyl group. In the embodiment, R22 is independently hydrogen. In the embodiment, R22 is unsubstituted C1-C It is 10 alkyl. In the embodiment, R22 is an unsubstituted C1-C8 alkyl. In this embodiment, R22 is an unsubstituted C1-C6 alkyl group. It is a substituted C1-C5 alkyl. In the embodiment, R22 is an unsubstituted C1-C4 alkyl. In the embodiment, R22 is an unsubstituted C1-C3 alkyl group. R22 is unsubstituted methyl. In the embodiment, R22 is unsubstituted ethyl. In the embodiment, In this embodiment, R22 is an unsubstituted propyl. In the embodiment, R22 is unsubstituted n-butyl. It is substituted t-butyl. In the embodiment, R22 is unsubstituted 2-butyl. In the embodiment R22 is unsubstituted isobutyl.

[0146] In this embodiment, each of R20, R21, and R22 is independently hydrogen or unsubstituted carbon. It is a 1-C3 alkyl group. In the embodiment, R20 is hydrogen, and each of R21 and R22 These are independently unsubstituted C1-C3 alkyl groups. In the embodiment, R21 is hydrogen, Each of R20 and R22 is independently an unsubstituted C1-C3 alkyl group. In the embodiment, R 22 is hydrogen, and each R20 and R21 is independently an unsubstituted C1-C3 alkyl. In the embodiment, R20, R21, and R22 are hydrogen. In the embodiment, R2 0 is an unsubstituted C1-C3 alkyl group, and R21 and R22 are hydrogen atoms. Embodiment Therefore, R21 is an unsubstituted C1-C3 alkyl group, and R20 and R22 are hydrogen atoms. In this embodiment, R22 is an unsubstituted C1-C3 alkyl, and R20 and R21 are It is hydrogen. In the embodiment, each of R20, R21, and R22 is independent and non-existent. It is a C1-C3 alkyl group.

[0147] In the embodiment, L2 is independently an unsubstituted C2-C24 alkylene. L2 is independently an unsubstituted C2-C22 alkylene. In the embodiment, L2 is independently And it is an unsubstituted C5-C22 alkylene. In the embodiment, L2 is independently an unsubstituted C1 It is an 0-C22 alkylene. In the embodiment, L2 is independently an unsubstituted C12-C22 alkylene. It is a lukilen. In the embodiment, L2 is independently an unsubstituted C10-C20 alkylene. In the embodiment, L2 is independently an unsubstituted C12-C20 alkylene. Embodiment Then, L2 is independently an unsubstituted C10-C18 alkylene. In the embodiment, L2 is Independently, it is an unsubstituted C12-C18 alkylene. In the embodiment, L2 is independently non It is a substituted C10-C16 alkylene. In the embodiment, L2 is independently an unsubstituted C12- It is a C16 alkylene. In the embodiment, L2 is independently an unsubstituted C14-C16 alkylene. It is a len. In the embodiment, L2 is independently an unsubstituted C14-C15 alkylene. In the embodiment, L2 is independently an unsubstituted C14 alkylene. In the embodiment, L2 is Independently, it is an unsubstituted C15 alkylene. In the embodiment, L2 is independently an unsubstituted C1 It is a 6-alkylene.

[0148] In the embodiment, L2 is independently an unsubstituted, unbranched C2-C24 alkylene. In this state, L2 is independently an unsubstituted, unbranched C2-C22 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched C5-C22 alkylene. In the embodiment, L2 is independently In this embodiment, L2 is an unsubstituted, unbranched C10-C22 alkylene. , an unsubstituted, unbranched C12-C22 alkylene. In the embodiment, L2 is independently, non-position It is a substituted, non-branched C10-C20 alkylene. In the embodiment, L2 is independently a non-substituted, non-branched alkylene. It is a branched C12-C20 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched C1 It is an 0-C18 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched C12-C 18 is alkylene. In the embodiment, L2 is independently unsubstituted unbranched C10-C16 It is a lukilen. In the embodiment, L2 is independently an unsubstituted, unbranched C12-C16 alkylene. In this embodiment, L2 is independently an unsubstituted, unbranched C14-C16 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched C14-C15 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched C14 alkylene. In the embodiment, L 2 is independently an unsubstituted, unbranched C15 alkylene. In the embodiment, L2 is independently It is an unsubstituted, unbranched C16 alkylene.

[0149] In the embodiment, L2 is independently an unsubstituted, unbranched saturated C2-C24 alkylene. In the application form, L2 is independently an unsubstituted, unbranched saturated C2-C22 alkylene. In this embodiment, L2 is independently an unsubstituted, unbranched saturated C5-C22 alkylene. In this embodiment, L2 is independently an unsubstituted, unbranched saturated C10-C22 alkylene. L2 is independently an unsubstituted, unbranched saturated C12-C22 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched saturated C10-C20 alkylene. In the embodiment, L 2 is independently an unsubstituted, unbranched saturated C12-C20 alkylene. In the embodiment, L2 Independently, L2 is an unsubstituted, unbranched saturated C10-C18 alkylene. In the embodiment, L2 is Independently, it is an unsubstituted, unbranched saturated C12-C18 alkylene. In the embodiment, L2 is independent In this embodiment, L2 is an unsubstituted, unbranched saturated C10-C16 alkylene. The unsubstituted, unbranched saturated C12-C16 alkylene is used. In the embodiment, L2 is independently It is an unsubstituted, unbranched saturated C14-C16 alkylene. In the embodiment, L2 is independently , an unsubstituted, unbranched saturated C14-C15 alkylene. In the embodiment, L2 is independently, It is an unsubstituted, unbranched saturated C14 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched alkylene. It is a branched saturated C15 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched saturated C1 It is a 6-alkylene.

[0150] In this embodiment, L2 is independently an unsubstituted, unbranched, unsaturated C2-C24 alkylene. In the embodiment, L2 is independently an unsubstituted, unbranched, unsaturated C2-C22 alkylene. In the application form, L2 is independently an unsubstituted, unbranched, unsaturated C5-C22 alkylene. Morphologically, L2 is independently an unsubstituted, unbranched, unsaturated C10-C22 alkylene. Morphologically, L2 is independently an unsubstituted, unbranched, unsaturated C12-C22 alkylene. Morphologically, L2 is independently an unsubstituted, unbranched, unsaturated C10-C20 alkylene. Morphologically, L2 is independently an unsubstituted, unbranched saturated C12-C20 alkylene. In this state, L2 is independently an unsubstituted, unbranched, unsaturated C10-C18 alkylene. In this state, L2 is independently an unsubstituted, unbranched, unsaturated C12-C18 alkylene. In this state, L2 is independently an unsubstituted, unbranched, unsaturated C10-C16 alkylene. In this embodiment, L2 is independently an unsubstituted, unbranched saturated C12-C16 alkylene. Therefore, L2 is independently an unsubstituted, unbranched, unsaturated C14-C16 alkylene. Embodiment Therefore, L2 is independently an unsubstituted, unbranched, unsaturated C14-C15 alkylene. Embodiment In this embodiment, L2 is independently an unsubstituted, unbranched, unsaturated C14 alkylene. 2 is independently an unsubstituted, unbranched, unsaturated C15 alkylene. In the embodiment, L2 is independently Therefore, it is an unsubstituted, unbranched, unsaturated C16 alkylene.

[0151] In the embodiment, the maximum dimension of L1 is less than 200 angstroms. The maximum dimension of L1 is less than 190 angstroms. In the embodiment, the maximum dimension of L1 The law is less than 180 angstroms. In the embodiment, the maximum dimension of L1 is 170 angstroms. It is less than angstroms. In the embodiment, the maximum dimension of L1 is 160 angstroms. It is less than. In the embodiment, the maximum dimension of L1 is less than 150 angstroms. In the embodiment, the maximum dimension of L1 is less than 140 angstroms. The maximum dimension of 1 is less than 130 angstroms. In the embodiment, the maximum dimension of L1 is , less than 120 angstroms. In the embodiment, the maximum dimension of L1 is 110 angstroms. It is less than 100 angstroms. In the embodiment, the maximum dimension of L1 is less than 100 angstroms. In this embodiment, the maximum dimension of L1 is less than 90 angstroms. Therefore, the maximum dimension of L1 is less than 80 angstroms. In the embodiment, the maximum of L1 The dimensions are less than 70 angstroms. In the embodiment, the maximum dimension of L1 is 60 angstroms. It is less than 50 angstroms. In the embodiment, the maximum dimension of L1 is less than 50 angstroms. In this embodiment, the maximum dimension of L1 is less than 40 angstroms. Therefore, the maximum dimension of L1 is less than 30 angstroms. In the embodiment, the maximum of L1 The dimensions are less than 20 angstroms. In the embodiment, the maximum dimension of L1 is 10 angstroms. It is less than a Gustrom.

[0152] In this embodiment, the maximum dimensions of each of L1A, L1B, L1C, L1D, and L1E are unique And it is less than 50 angstroms. In the embodiment, L1A, L1B, L1C, L The maximum dimensions of 1D and L1E are independently less than 40 angstroms. In the configuration, the maximum dimensions of L1A, L1B, L1C, L1D, and L1E are independent of each other. And it is less than 30 angstroms. In the embodiment, L1A, L1B, L1C, L1D The maximum dimensions of each of the L1E components are independently less than 20 angstroms. In this configuration, the maximum dimensions of L1A, L1B, L1C, L1D, and L1E are independent of each other. It is less than 10 angstroms.

[0153] In this embodiment, the maximum dimension of L1A is independently less than 50 angstroms. In this embodiment, the maximum dimension of L1A is independently less than 40 angstroms. The maximum dimension of L1A is independently less than 30 angstroms. In the embodiment, L The maximum dimension of 1A is independently less than 20 angstroms. In the embodiment, L1A The maximum dimensions are independently less than 10 angstroms.

[0154] In this embodiment, the maximum dimension of L1B is independently less than 50 angstroms. In this embodiment, the maximum dimension of L1B is independently less than 40 angstroms. The maximum dimension of L1B is independently less than 30 angstroms. In the embodiment, L The maximum dimension of 1B is independently less than 20 angstroms. In the embodiment, L1B The maximum dimensions are independently less than 10 angstroms.

[0155] In this embodiment, the maximum dimension of L1C is independently less than 50 angstroms. In the embodiment, the maximum dimension of L1C is independently less than 40 angstroms. The maximum dimension of L1C is independently less than 30 angstroms. In the embodiment, L The maximum dimension of 1C is independently less than 20 angstroms. In the embodiment, L1C The maximum dimensions are independently less than 10 angstroms.

[0156] In this embodiment, the maximum dimension of L1D is independently less than 50 angstroms. In this embodiment, the maximum dimension of L1D is independently less than 40 angstroms. The maximum dimension of L1D is independently less than 30 angstroms. In the embodiment, L The maximum dimension of 1D is independently less than 20 angstroms. In the embodiment, L1D The maximum dimensions are independently less than 10 angstroms.

[0157] In this embodiment, the maximum dimension of L1E is independently less than 50 angstroms. In this embodiment, the maximum dimension of L1E is independently less than 40 angstroms. The maximum dimension of L1E is independently less than 30 angstroms. In the embodiment, L The maximum dimension of 1E is independently less than 20 angstroms. In the embodiment, L1E The maximum dimensions are independently less than 10 angstroms.

[0158] In the embodiment, nucleic acid (A) is an oligonucleotide. In the embodiment, one L1 A is bonded to the 3' carbon of the oligonucleotide. In this embodiment, one L1A is oligonucleotide It binds to the 3' nitrogen of a gonucleotide (for example, the 3' nitrogen of the morpholino moiety). In this configuration, one L1A is bonded to the 5' carbon of the oligonucleotide. In this embodiment, 1 One L1A is the 6' carbon of the oligonucleotide (for example, the 6' carbon of the morpholino moiety). It bonds with the 2' carbon of the oligonucleotide. In this embodiment, one L1A bonds with the 2' carbon of the oligonucleotide. In this embodiment, one L1A binds to a nucleic acid base of the oligonucleotide.

[0159] In the embodiment, at least one L1A is the 3' carbon of the oligonucleotide at its 3' end. It binds to. In the embodiment, at least one L1A has an oligonucleotide at its 3' end. It binds to the 3' nitrogen of the cydide (for example, the 3' nitrogen of the morpholino moiety). In the embodiment, At the very least, one L1A molecule will bond to the 5' carbon of an oligonucleotide at its 5' end. In the application form, at least one L1A has a 5' end at the 6' carbon of the oligonucleotide. It bonds to (for example, the 6' carbon of the morpholino portion).

[0160] In the embodiment, nucleic acid (A) is a double-stranded oligonucleotide. In the embodiment, one L1A is bonded to the 3' carbon of the double-stranded oligonucleotide. In the embodiment, one L 1A binds to the 3' carbon of a double-stranded oligonucleotide at one of its 3' ends. In the application form, one L1A has a double-stranded oligonucleotide at the 3' end of its antisense chain. It bonds to the 3' carbon of the do. In the embodiment, one L1A is at the 3' end of its cysnes chain. It binds to the 3' carbon of a double-stranded oligonucleotide.

[0161] In this embodiment, one L1A has a double-stranded oligonucleotide at either of its 3' ends. It binds to the 3' nitrogen (for example, the 3' nitrogen of the morpholino moiety). In one embodiment, one L1A is the 3' nitrogen of the double-stranded oligonucleotide at the 3' end of its antisense chain (for example) If so, it bonds with the 3' nitrogen of the morpholino moiety. In the embodiment, one L1A is its se At the 3' end of the lance chain, the 3' nitrogen of the double-stranded oligonucleotide (for example, the morpholino portion) It binds to the 3' nitrogen.

[0162] In this embodiment, one L1A has a double-stranded oligonucleotide at either of its 5' ends. It bonds to the 5' carbon. In one embodiment, one L1A is the 5' end of its antisense chain. It then bonds to the 5' carbon of the double-stranded oligonucleotide. In this embodiment, one L1A is The sense strand's 5' end binds to the 5' carbon of the double-stranded oligonucleotide.

[0163] In one embodiment, one L1A has a double-stranded oligonucleotide at either of its 5' ends. It bonds to the 6' carbon of the do (for example, the 6' carbon of the morpholino moiety). In one embodiment, L1A is the 6' carbon of the double-stranded oligonucleotide at the 5' end of its antisense chain (e.g., For example, it bonds to the 6' carbon of the morpholino moiety. In this embodiment, one L1A is The 6' carbon of the double-stranded oligonucleotide at the 5' end of the sense chain (for example, the morpholino portion) It bonds with the 6' carbon.

[0164] In this embodiment, one L1A is bonded to the 2' carbon of a double-stranded oligonucleotide. In the application form, one L1A has 5 double-stranded oligonucleotides at either of its 2' ends. 'It bonds to carbon. In this embodiment, one L1A is bonded to the 2' carbon at the 5' end of the sense chain. Combine. In this embodiment, one L1A is bonded to the 2' carbon at the 5' end of the antisense chain. In this embodiment, one L1A has a double-stranded oligonucleotide at either of its 3' ends. It bonds to the 2' carbon of the sense chain. In this embodiment, one L1A is bonded to the 2' carbon at the 3' end of the sense chain. It bonds with the element. In one embodiment, one L1A is bonded to the 2' carbon at the 3' end of the antisense chain. Combine.

[0165] In this embodiment, one L1A binds to a nucleic acid base of a double-stranded oligonucleotide. In the application form, one L1A binds to the nucleic acid base of the sense strand of the double-stranded oligonucleotide. In this embodiment, one L1A is the nucleic acid of the antisense strand of the double-stranded oligonucleotide. It binds to a base. In this embodiment, one L1A is double-stranded at either of its 3' ends. It binds to the nucleic acid base of a nucleotide. In one embodiment, one L1A is its antisene It binds to the nucleic acid base of the double-stranded oligonucleotide at the 3' end of the chain. In this embodiment, one L1A binds to the nucleic acid base of the double-stranded oligonucleotide at the 3' end of its sense strand. In this embodiment, one L1A has a double-stranded oligonucleotide at either of its 5' ends. It binds to the nucleic acid base. In one embodiment, one L1A is at the 5' end of its antisense strand. It binds to the nucleic acid base of the double-stranded oligonucleotide. In this embodiment, one L1A is It binds to the nucleic acid base of the double-stranded oligonucleotide at the 5' end of its sense strand.

[0166] In the embodiment, nucleic acid (A) is a single-stranded oligonucleotide. In the embodiment, one L1A of this molecule binds to the 3' carbon of a single-stranded oligonucleotide at its 3' end.

[0167] In this embodiment, one L1A is at the 3' end of a single-stranded oligonucleotide. It binds to the 3' nitrogen of a nucleotide (for example, the 3' nitrogen of the morpholino portion).

[0168] In this embodiment, one L1A is bonded to the 5' carbon of a single-stranded oligonucleotide at its 5' end. To combine.

[0169] In the embodiment, one L1A is the 6' carbon of a single-stranded oligonucleotide at its 5' end (e.g.) For example, it bonds to the 6' carbon of the morpholino portion.

[0170] In this embodiment, one L1A is bonded to the 2' carbon of a single-stranded oligonucleotide. In the application form, L1A is bonded to the 2' carbon of a single-stranded oligonucleotide at its 5' end. In this embodiment, one L1A has the 2' carbon of a single-stranded oligonucleotide at its 3' end. It combines with it.

[0171] In this embodiment, one L1A binds to a nucleic acid base of a single-stranded oligonucleotide. In this application, one L1A binds to a nucleic acid base of a single-stranded oligonucleotide at its 3' end. In this embodiment, one L1A has a nucleic acid base of a single-stranded oligonucleotide at its 5' end. Combine.

[0172] In this embodiment, L1A is independently -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-, substitution or This is an unsubstituted alkylene, or a substituted or unsubstituted heteroalkylene. In the embodiment, L1A is independent of -O-, -C(O)-, -C(O)O-, or -OC(O)-. Yes. In the embodiment, L1A is independently -OPO2-O-, -OP(O)(S)-O It is -, -OP(O)(CH3)-O-, or -OP(S)(CH3)-O-. In this embodiment, L1A is independently -OP(O)(N(CH3)2)-N-, -OP (O)(N(CH3)2)-O-, -OP(S)(N(CH3)2)-N-, or - It is OP(S)(N(CH3)2)-O-. In the embodiment, L1A is independently -P (O)(N(CH3)2)-N-, -P(O)(N(CH3)2)-O-, -P(S)( It is N(CH3)2)-N- or -P(S)(N(CH3)2)-O-.

[0173] In the embodiment, L1A is independently a substituted or unsubstituted C1-C20 alkylene. In the embodiment, L1A is independently a substituted or unsubstituted C1-C12 alkylene. In the application form, L1A is independently a substituted or unsubstituted C1-C8 alkylene. In this embodiment, L1A is independently a substituted or unsubstituted C1-C6 alkylene. In this embodiment, L1A is independently a substituted or unsubstituted C1-C4 alkylene. L1A is independently a substituted or unsubstituted C1-C2 alkylene.

[0174] In the embodiment, L1A is independently a substituted or unsubstituted 2-20 member heteroalkylene. In the embodiment, L1A is independently a substituted or unsubstituted 2- to 16-membered heteroalkylene. Yes. In the embodiment, L1A is independently a substituted or unsubstituted 2- to 12-membered heteroalkylene. In this embodiment, L1A is independently substituted or unsubstituted 2-10 member heteroalkylates. In this embodiment, L1A is independently substituted or unsubstituted 2-8 member heteroalkylates. In this embodiment, L1A is independently substituted or unsubstituted 2-6 member heteroalkylates. In this embodiment, L1A is independently substituted or unsubstituted 2-4 member heteroalkylates. In this embodiment, L1A is independently substituted or unsubstituted 2-3 member heteroalkylates. It is.

[0175] In this embodiment, L1A is independently, [ka] In this embodiment, L1A is independently -OPO2-O-. In this embodiment, L 1A is independently -OP(O)(S)-O-. In the embodiment, L1A is independently , is -O-. In this embodiment, L1A is independently -S-.

[0176] In this embodiment, L1A is bonded to the 3' nitrogen of the morpholino moiety. L1A is independently -C(O)-. In this embodiment, L1A is the morpholino portion It bonds to the 6' carbon. In the embodiment, L1A is independently -OP(O)(N(CH3 )2)-N-. In this embodiment, L1A is independently -OP(O)(N(CH3) 2) -O-. In this embodiment, L1A is independently -P(O)(N(CH3)2)- It is N-. In the embodiment, L1A is independently -P(O)(N(CH3)2)-O- be.

[0177] In this embodiment, L1B is independently a substituted or unsubstituted alkylene, or substituted or L1B is an unsubstituted heteroalkylene. In the embodiment, L1B is independently substituted or unsubstituted. It is a C1-C20 alkylene. In the embodiment, L1B is independently substituted or unsubstituted C It is a 1-C12 alkylene. In the embodiment, L1B is independently a substituted or unsubstituted C1 -C8 alkylene. In the embodiment, L1B is independently substituted or unsubstituted C1-C 6. Alkylene. In the embodiment, L1B is independently substituted or unsubstituted C1-C4 It is a lukilen. In the embodiment, L1B is independently a substituted or unsubstituted C1-C2 alkyl It's Ren.

[0178] In the embodiment, L1B is independently a substituted or unsubstituted 2-20 member heteroalkylene. In the embodiment, L1B is independently a substituted or unsubstituted 2- to 16-membered heteroalkylene. Yes. In the embodiment, L1B is independently a substituted or unsubstituted 2- to 12-membered heteroalkylene. In this embodiment, L1B is independently a substituted or unsubstituted 2-10 member heteroalkylate. In this embodiment, L1B is independently a substituted or unsubstituted 2-8 member heteroalkylate. In this embodiment, L1B is independently a substituted or unsubstituted 2-6 member heteroalkylate. In this embodiment, L1B is independently a substituted or unsubstituted 2-4 member heteroalkylate. In this embodiment, L1B is independently a substituted or unsubstituted 2-3 member heteroalkylate. It is.

[0179] In this embodiment, L1B is independently -L10-NH-C(O)- or -L10-C( It is O)-NH-. L10 is a substituted or unsubstituted alkylene.

[0180] In the embodiment, L10 is independently a substituted or unsubstituted alkylene (e.g., C1-C2 (0, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L10 is independently a substituted alkylene (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L10 is independently unsubstituted alkylene (e.g., C1-C20, C1-C12, C1-C 8, C1-C6, C1-C4, or C1-C2). In this embodiment, L10 is independent The C1-C20 alkylene is either substituted or unsubstituted. In the embodiment, L10 is independently The substituted C1-C20 alkylene is a hydroxyl group. In the embodiment, L10 is independently a hydroxyl group. It is an (OH)-substituted C1-C20 alkylene. In the embodiment, L10 is independently Hydro It is a xymethyl-substituted C1-C20 alkylene. In the embodiment, L10 is independently non-existent. It is a C1-C20 alkylene. In the embodiment, L10 is independently substituted or unsubstituted. It is a C1-C12 alkylene. In the embodiment, L10 is independently a substituted C1-C12 alkylene. It is ruquilen. In the embodiment, L10 is independently a hydroxy(OH) substituted C1-C1 It is an alkylene. In the embodiment, L10 is independently a hydroxymethyl-substituted C1-C It is a 12-alkylene. In the embodiment, L10 is independently an unsubstituted C1-C12 alkylene. In this embodiment, L10 is independently a substituted or unsubstituted C1-C8 alkylene. Yes. In the embodiment, L10 is independently a substituted C1-C8 alkylene. In this embodiment, L10 is independently a hydroxy(OH)-substituted C1-C8 alkylene. Therefore, L10 is independently a hydroxymethyl-substituted C1-C8 alkylene. Embodiment Then, L10 is independently an unsubstituted C1-C8 alkylene. In the embodiment, L10 is Independently, it is a substituted or unsubstituted C1-C6 alkylene. In the embodiment, L10 is independent And it is a substituted C1-C6 alkylene. In the embodiment, L10 is independently a hydroxyl It is an (OH)-substituted C1-C6 alkylene. In the embodiment, L10 is independently a hydroxyl It is a methyl-substituted C1-C6 alkylene. In the embodiment, L10 is independently an unsubstituted C It is a 1-C6 alkylene. In the embodiment, L10 is independently a substituted or unsubstituted C1- It is a C4 alkylene. In the embodiment, L10 is independently a substituted C1-C4 alkylene. Yes. In the embodiment, L10 is independently a hydroxy(OH)-substituted C1-C4 alkylene. In this embodiment, L10 is independently a hydroxymethyl-substituted C1-C4 alkylene. In this embodiment, L10 is independently an unsubstituted C1-C4 alkylene. In this embodiment, L10 is independently a substituted or unsubstituted C1-C2 alkylene. In this embodiment, L10 is independently a substituted C1-C2 alkylene. The result is a hydroxy(OH)-substituted C1-C2 alkylene. In the embodiment, L10 is German In particular, it is a hydroxymethyl-substituted C1-C2 alkylene. In the embodiment, L10 is In other words, it is an unsubstituted C1-C2 alkylene.

[0181] In this embodiment, L1B is independently, [ka] In this embodiment, L1B is independently [ka] That is the case.

[0182] In this embodiment, L1B is independently, [ka] w1 is an integer between 0 and 10. w2 is an integer between 0 and 5. w3 is an integer between 0 and 5. w4 is an integer between 0 and 5.

[0183] In this embodiment, L1B is independently, [ka] w1, w2, w3, and w4 are as described above.

[0184] In this embodiment, w1 is 0. In this embodiment, w1 is 1. In this embodiment, w1 is 2. In the embodiment, w1 is 3. In the embodiment, w1 is 4. In this embodiment, w1 is 5. In this embodiment, w1 is 6. In this 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 In this embodiment, w2 is 1. In this embodiment, w2 is 2. In this embodiment, w2 is 3. In the embodiment, w2 is 4. In the embodiment, w2 is 5. In the embodiment In this embodiment, w3 is 0. In this embodiment, w3 is 1. In this embodiment, w3 is 2. In the embodiment, w3 is 3. In the embodiment, w3 is 4. In the embodiment In this embodiment, w3 is 5. In this embodiment, w4 is 0. In this embodiment, w4 is 1. In the embodiment, w4 is 2. In the embodiment, w4 is 3. In the embodiment In this embodiment, w4 is 4.

[0185] In this embodiment, L1B is independently, [ka] That is the case.

[0186] In this embodiment, L1B is independently, [ka] In this embodiment, L1B is independently [ka] In this embodiment, w4 is 0. In this embodiment, w1 is 1. Embodiment Then, w1 is 2. In the embodiment, w2 is 3. In the embodiment, w4 is 0 In this embodiment, w1 is 2. In this embodiment, w4 is 0 and w1 is 3. Morphologically, w4 is 0 and w1 is 4.

[0187] In this embodiment, L1B is independently, [ka] In this embodiment, L1B is independently [ka] That is the case.

[0188] In this embodiment, -L1A-L1B- are independently -O-L10-NH-C(O)- and It is -O-L10-C(O)-NH-. L10 is independently substituted or unsubstituted. Chelen, substituted or unsubstituted heteroalkylene, or substituted or unsubstituted heteroalkylene It is nilen. In the embodiment, -L1A-L1B- is independently -O-L10-NH-C (O)-. In this embodiment, -L1A-L1B- are independently -O-L10-C(O It is )-NH-.

[0189] In the embodiment, L10 is independently a substituted or unsubstituted alkylene (e.g., C1-C2 (0, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L10 is independently a substituted alkylene (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L10 is independently unsubstituted alkylene (e.g., C1-C20, C1-C12, C1-C 8, C1-C6, C1-C4, or C1-C2). In this embodiment, L10 is independent The C1-C20 alkylene is either substituted or unsubstituted. In the embodiment, L10 is independently The substituted C1-C20 alkylene is a hydroxyl group. In the embodiment, L10 is independently a hydroxyl group. It is an (OH)-substituted C1-C20 alkylene. In the embodiment, L10 is independently Hydro It is a xymethyl-substituted C1-C20 alkylene. In the embodiment, L10 is independently non-existent. It is a C1-C20 alkylene. In the embodiment, L10 is independently substituted or unsubstituted. It is a C1-C12 alkylene. In the embodiment, L10 is independently a substituted C1-C12 alkylene. It is ruquilen. In the embodiment, L10 is independently a hydroxy(OH) substituted C1-C1 It is an alkylene. In the embodiment, L10 is independently a hydroxymethyl-substituted C1-C It is a 12-alkylene. In the embodiment, L10 is independently an unsubstituted C1-C12 alkylene. In this embodiment, L10 is independently a substituted or unsubstituted C1-C8 alkylene. Yes. In the embodiment, L10 is independently a substituted C1-C8 alkylene. In this embodiment, L10 is independently a hydroxy(OH)-substituted C1-C8 alkylene. Therefore, L10 is independently a hydroxymethyl-substituted C1-C8 alkylene. Embodiment In this embodiment, L10 is independently a substituted or unsubstituted C1-C8 alkylene. L10 is independently a substituted or unsubstituted C5-C8 alkylene. In the embodiment, L 10 is independently a substituted C5-C8 alkylene. In the embodiment, L10 is independently It is a hydroxy(OH)-substituted C5-C8 alkylene. In the embodiment, L10 is independently , a hydroxymethyl-substituted C5-C8 alkylene. In the embodiment, L10 is independently , unsubstituted C5-C8 alkylene. In the embodiment, L10 is independently substituted or unsubstituted. It is a substituted C1-C6 alkylene. In the embodiment, L10 is independently a substituted C1-C6 alkylene. It is ruquilen. In the embodiment, L10 is independently a hydroxy(OH) substituted C1-C6 It is an alkylene. In the embodiment, L10 is independently a hydroxymethyl-substituted C1-C6 It is an alkylene. In the embodiment, L10 is independently an unsubstituted C1-C6 alkylene. In the embodiment, L10 is independently a substituted or unsubstituted C1-C4 alkylene. In the embodiment, L10 is independently a substituted C1-C4 alkylene. In the embodiment, L 10 is independently a hydroxy(OH)-substituted C1-C4 alkylene. In the embodiment, L10 is independently a hydroxymethyl-substituted C1-C4 alkylene. In the embodiment, L10 is independently an unsubstituted C1-C4 alkylene. In the embodiment, L10 is independently And it is a substituted or unsubstituted C1-C2 alkylene. In the embodiment, L10 is independently It is a substituted C1-C2 alkylene. In the embodiment, L10 is independently a hydroxyl(OH) ) is a substituted C1-C2 alkylene. In the embodiment, L10 is independently a hydroxymethyl It is a substituted C1-C2 alkylene. In the embodiment, L10 is independently an unsubstituted C1-C It is a 2-alkylene.

[0190] In this embodiment, -L1A-L1B- are independent of each other. [ka] In this embodiment, -L1A-L1B- are independent of each other. [ka] In this embodiment, -L1A-L1B- are independent of each other. [ka] In this embodiment, -L1A-L1B- are independent of each other. [ka] That is the case.

[0191] In this embodiment, -L1A-L1B- are independently -OPO2-O-L10-NH-C( O)-, -OP(O)(S)-O-L10-NH-C(O)-, -OPO2-O-L10 It is -C(O)-NH- or -OP(O)(S)-O-L10-C(O)-NH-. In the embodiment, L10 is independently a substituted or unsubstituted alkylene. -L1A-L1B- independently, -OPO2-O-L10-NH-C(O)- or - It is OP(O)(S)-O-L10-NH-C(O)-. In the embodiment, -L1A-L 1B- is independently -OPO2-O-L10-C(O)-NH- or -OP(O)(S )-O-L10-C(O)-NH-. In the embodiment, L10 is independently substituted or is an unsubstituted alkylene. In the embodiment, L10 is independently a substituted or unsubstituted C5- It is a C8 alkylene. In the embodiment, L10 is independently a substituted C5-C8 alkylene. Yes. In the embodiment, L10 is independently a hydroxy(OH)-substituted C5-C8 alkylene. In this embodiment, L10 is independently a hydroxymethyl-substituted C5-C8 alkylene. In this embodiment, L10 is independently an unsubstituted C5-C8 alkylene.

[0192] In this embodiment, -L1A-L1B- are independent of each other. [ka] That is the case.

[0193] In this embodiment, -L1A-L1B- are independent of each other. [ka] In this embodiment, -L1A-L1B- are independent of each other. [ka] In this embodiment, -L1A-L1B- are independent of each other. [ka] In this embodiment, -L1A-L1B- are independent of each other. [ka] In this embodiment, -L1A-L1B- are independent of each other. [ka] That is the case.

[0194] In this embodiment, -L1A-L1B- are independent of each other. [ka] It then bonds to the 3' carbon of the oligonucleotide. In this embodiment, -L1A-L1B- independently bond to the 3' carbon of the oligonucleotide. ru, [ka] In this embodiment, -L1A-L1B- are independently the 3' carbon of the oligonucleotide. It combines with, [ka] That is the case.

[0195] In this embodiment, -L1A-L1B- are independent of each other. [ka] It binds to the 3' nitrogen of the oligonucleotide (for example, the 3' nitrogen of the morpholino portion). do. In the embodiment, -L1A-L1B- independently represent the 3' nitrogen of the oligonucleotide (e.g., , it binds to the 3' nitrogen of the morpholino portion, [ka] In this embodiment, -L1A-L1B- independently represents the 3' nitrogen of the oligonucleotide. (For example, the 3' nitrogen of the morpholino portion) [ka] That is the case.

[0196] In this embodiment, -L1A-L1B- are independent of each other. [ka] It is bonded to the 5' carbon of the oligonucleotide. In the embodiment, -L1A-L1B- It independently bonds to the 5' carbon of the oligonucleotide. [ka] In this embodiment, -L1A-L1B- are independently the 5' carbon of the oligonucleotide. It combines with, [ka] That is the case.

[0197] In embodiments in which the oligonucleotide includes a morpholino moiety, L1A is independently -P It is (O)(N(CH3)2)-N- or -P(O)(N(CH3)2)-O-. In the embodiment, L1B is a substituted or unsubstituted heterocycloalkyl. L1B is a substituted heterocycloalkyl. In the embodiment, L1B is an unsubstituted heterocycloalkyl. It is a chloroalkyl compound. In the embodiment, L1B is a substituted or unsubstituted piperidinylene. In the embodiment, L1B is a substituted piperidine. In the embodiment, L1B is a non-substituted piperidine. It is a substituted piperidinerine. In the embodiment, L1B is a substituted or unsubstituted piperidinerine. Yes. In the embodiment, L1B is a substituted piperazinerene. In the embodiment, L1B is It is an unsubstituted piperazinerene. In the embodiment, -L1A-L1B- are independently oligonucleotides. It bonds to the 6' carbon of the creotide (for example, the 6' carbon of the morpholino moiety), [ka] In this embodiment, -L1A-L1B- are independently the 6' carbon of the oligonucleotide. (For example, the 6' carbon of the morpholino portion) [ka] In this embodiment, -L1A-L1B- are independently the 6' carbon of the oligonucleotide. (For example, the 6' carbon of the morpholino portion) [ka] That is the case.

[0198] In the embodiment, -L1A-L1B- independently bind to the nucleic acid base of the oligonucleotide. In this embodiment, -L1A-L1B- are independent of each other. [ka] It binds to the nucleic acid base of an oligonucleotide.

[0199] In this embodiment, L1C is independently a substituted or unsubstituted alkylene, or substituted or L1D is an unsubstituted heteroalkylene, and L1D is independently bound, substituted, or unsubstituted alkyl Len, substituted or unsubstituted heteroalkylene, substituted or unsubstituted arylene, or substituted heteroalkylene, substituted or unsubstituted arylene, or substituted heteroalkylene, substituted or unsubstituted heteroalkylene It is a substituted or unsubstituted heteroarylene, where L1E is independently bound, substituted, or unsubstituted. It is a converted heteroalkylene, or -NHC(O)-.

[0200] In this embodiment, L1C is independently a substituted or unsubstituted alkylene, or substituted or L1C is an unsubstituted heteroalkylene. In the embodiment, L1C is independently substituted or unsubstituted. It is an alkylene. In the embodiment, L1C is independently substituted or unsubstituted C1-C10 The molecule is an alkylene, or a substituted or unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L1C is independently a substituted or unsubstituted C1-C10 alkylene. In the embodiment, L1C is independently a substituted C1-C10 alkylene. In the embodiment, L 1C is independently an unsubstituted C1-C10 alkylene. In the embodiment, L1C is independently The C1-C8 alkylene is either substituted or unsubstituted. In the embodiment, L1C is independently It is a substituted C1-C8 alkylene. In the embodiment, L1C is independently an unsubstituted C1-C8 alkylene. It is an alkylene. In the embodiment, L1C is independently a substituted or unsubstituted C3-C8 alkylene. It is a kylene. In the embodiment, L1C is independently a substituted C3-C8 alkylene. In the embodiment, L1C is independently an unsubstituted C3-C8 alkylene. In the embodiment, L 1C is independently a substituted or unsubstituted C3-C7 alkylene. In the embodiment, L1C Independently, is a substituted C3-C7 alkylene. In the embodiment, L1C is independently non-substituted. It is a C3-C7 alkylene.

[0201] In the embodiment, L1C is independently R1C-substituted or unsubstituted alkylene. Morphologically, L1C is independently either R1C-substituted or unsubstituted C1-C10 alkylene. In the embodiment, L1C is independently an R1C-substituted C1-C10 alkylene. In its morphology, L1C is independently an unsubstituted C1-C10 alkylene. In the embodiment, L 1C is independently an R1C-substituted or unsubstituted C1-C8 alkylene. In the embodiment, L1C is independently an R1C-substituted C1-C8 alkylene. In the embodiment, L1C Independently, is an unsubstituted C1-C8 alkylene. In the embodiment, L1C is independently R It is a 1C-substituted or unsubstituted C3-C8 alkylene. In the embodiment, L1C is independently , R1C-substituted C3-C8 alkylene. In the embodiment, L1C is independently unsubstituted. It is a C3-C8 alkylene. In the embodiment, L1C is independently R1C-substituted or non-substituted. It is a substituted C3-C7 alkylene. In the embodiment, L1C is independently R1C-substituted C3 -C7 alkylene. In the embodiment, L1C is independently an unsubstituted C3-C7 alkylene. It is.

[0202] In the embodiment, L1C is independently a substituted or unsubstituted heteroalkylene. In this state, L1C is independently a substituted or unsubstituted 2- to 10-membered heteroalkylene. Morphologically, L1C is independently a substituted 2- to 10-membered heteroalkylene. In the embodiment, L1C is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L1C is They are independently substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L1C is Independently, they are substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1C is independently non It is a substituted 2- to 8-membered heteroalkylene. In the embodiment, L1C is independently substituted or non-substituted. It is a substituted 5-8 member heteroalkylene. In the embodiment, L1C is independently a substituted 5-8 member It is a heteroalkylene. In the embodiment, L1C is independently an unsubstituted 5-8 member heteroalkylene. It is Kiren.

[0203] In the embodiment, L1C is independently an R1C-substituted or unsubstituted heteroalkylene. In the embodiment, L1C is independently R1C-substituted or unsubstituted 2- to 10-membered heteroalkyl It is Len. In the embodiment, L1C is independently R1C-substituted 2-10 member heteroalkyl In this embodiment, L1C is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L1C is independently R1C-substituted or unsubstituted 2-8 member heteroalkylates. In this embodiment, L1C is independently R1C-substituted 2- to 8-membered heteroalkylene. Yes. In the embodiment, L1C is independently an unsubstituted 2- to 8-membered heteroalkylene. Morphologically, L1C is independently an R1C-substituted or unsubstituted 5- to 8-membered heteroalkylene. In this embodiment, L1C is independently an R1C-substituted 5- to 8-membered heteroalkylene. In this embodiment, L1C is independently an unsubstituted 5- to 8-membered heteroalkylene.

[0204] R1C is independently a substituted or unsubstituted alkyl group, or a substituted or unsubstituted heteroalkyl group. substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted Alternatively, it may be an unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0205] In the embodiment, L1D is independently a bound, substituted or unsubstituted alkylene, or a substituted alkylene. Alternatively, it is an unsubstituted heteroalkylene. In the embodiment, L1D is independently a bond. .

[0206] In this embodiment, L1D is independently a substituted or unsubstituted alkylene, or substituted or L1D is an unsubstituted heteroalkylene. In the embodiment, L1D is independently substituted or unsubstituted. It is an alkylene. In the embodiment, L1D is independently substituted or unsubstituted C1-C10 The alkylene, or a substituted or unsubstituted 2- to 10-membered heteroalkylene. In this embodiment, L1D is independently a substituted or unsubstituted C1-C10 alkylene. L1D is independently a substituted C1-C10 alkylene. In the embodiment, L1D is independently And it is an unsubstituted C1-C10 alkylene. In the embodiment, L1D is independently substituted or is an unsubstituted C1-C8 alkylene. In the embodiment, L1D is independently a substituted C1- It is a C8 alkylene. In the embodiment, L1D is independently an unsubstituted C1-C8 alkylene. In this embodiment, L1D is independently a substituted or unsubstituted C3-C8 alkylene. In the embodiment, L1D is independently a substituted C3-C8 alkylene. L1D is independently an unsubstituted C3-C8 alkylene. In the embodiment, L1D is independently And it is a substituted or unsubstituted C3-C7 alkylene. In the embodiment, L1D is independently , a substituted C3-C7 alkylene. In the embodiment, L1D is independently an unsubstituted C3-C It is an alkylene.

[0207] In the embodiment, L1D is independently R1D-substituted or unsubstituted alkylene. Morphologically, L1D is independently either R1D-substituted or unsubstituted C1-C10 alkylene. In the embodiment, L1D is independently R1D-substituted C1-C10 alkylene. In its morphology, L1D is independently an unsubstituted C1-C10 alkylene. In the embodiment, L 1D is independently an R1D-substituted or unsubstituted C1-C8 alkylene. In the embodiment, L1D is independently an R1D-substituted C1-C8 alkylene. In the embodiment, L1D Independently, is an unsubstituted C1-C8 alkylene. In the embodiment, L1D is independently R It is a 1D-substituted or unsubstituted C3-C8 alkylene. In the embodiment, L1D is independently , R1D-substituted C3-C8 alkylene. In the embodiment, L1D is independently unsubstituted. It is a C3-C8 alkylene. In the embodiment, L1D is independently R1D-substituted or non-substituted. It is a substituted C3-C7 alkylene. In the embodiment, L1D is independently R1D-substituted C3 -C7 alkylene. In the embodiment, L1D is independently an unsubstituted C3-C7 alkylene. It is.

[0208] In the embodiment, L1D is independently a substituted or unsubstituted heteroalkylene. In this state, L1D is independently a substituted or unsubstituted 2- to 10-membered heteroalkylene. Morphologically, L1D is independently a substituted 2- to 10-membered heteroalkylene. In the embodiment, L1D is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L1D is They are independently substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L1D is Independently, they are substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1D is independently non It is a substituted 2- to 8-membered heteroalkylene. In the embodiment, L1D is independently substituted or non-substituted. It is a substituted 5-8 member heteroalkylene. In the embodiment, L1D is independently a substituted 5-8 member It is a heteroalkylene. In the embodiment, L1D is independently an unsubstituted 5- to 8-membered heteroalkylene. It is Kiren.

[0209] In the embodiment, L1D is independently R1D-substituted or unsubstituted heteroalkylene. In the embodiment, L1D is independently R1D-substituted or unsubstituted 2- to 10-membered heteroalkyl It is Len. In the embodiment, L1D is independently R1D-substituted 2-10 member heteroalkyl In this embodiment, L1D is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L1D is independently R1D-substituted or unsubstituted 2-8 member heteroalkylates. In this embodiment, L1D is independently R1D-substituted 2- to 8-membered heteroalkylene. Yes. In the embodiment, L1D is independently an unsubstituted 2- to 8-membered heteroalkylene. Morphologically, R1D-substituted or unsubstituted 5- to 8-membered heteroalkylenes. In embodiments, L1D These are independently R1D-substituted 5- to 8-membered heteroalkylenes. In the embodiment, L1D is independently In short, it is an unsubstituted 5- to 8-membered heteroalkylene.

[0210] In the embodiment, L1D is independently a substituted or unsubstituted arylene. L1D is independently substituted or unsubstituted arylene (e.g., C6-C12, C6-C1 0, or phenyl). In embodiments, L1D is independently a substituted arylene (e.g. For example, C6-C12, C6-C10, or phenyl. In this embodiment, L1D is German And, using unsubstituted arylenes (e.g., C6-C12, C6-C10, or phenyl) Yes. In the embodiment, L1D is independently a substituted or unsubstituted C6-C12 arylene. In the embodiment, L1D is independently a substituted C6-C12 arylene. In this embodiment, L1D is independently an unsubstituted C6-C12 arylene. Independently, these are substituted or unsubstituted C6-C10 arylenes. In the embodiment, L1D is Independently, it is a substituted C6-C10 arylene. In the embodiment, L1D is independently non-substituted. It is a substitution C6-C10 arylene. In the embodiment, L1D is independently substituted or unsubstituted. It is phenylene. In the embodiment, L1D is independently a substituted phenylene. Embodiment In this embodiment, L1D is independently an unsubstituted phenylene. It is a substituted or unsubstituted biphenylene. In the embodiment, L1D is independently a substituted biphenylene. It is len. In the embodiment, L1D is independently an unsubstituted biphenylene. In this embodiment, L1D is independently a substituted or unsubstituted naphthylene. In this embodiment, L1D is independently an unsubstituted naphthylene. be.

[0211] In the embodiment, L1D is independently R1D-substituted or unsubstituted arylene (e.g., C (6-C12, C6-C10, or phenyl). In the embodiment, L1D is independently , R1D-substituted arylene (e.g., C6-C12, C6-C10, or phenyl) Yes. In the embodiment, L1D is independently an unsubstituted arylene (e.g., C6-C12, C It is 6-C10, or phenyl). In the embodiment, L1D is independently R1D-substituted. Alternatively, it is an unsubstituted C6-C12 arylene. In the embodiment, L1D is independently R1D - Substituted C6-C12 arylene. In the embodiment, L1D is independently unsubstituted C6- C12 arylene is used. In the embodiment, L1D is independently R1D-substituted or non-substituted. It is a substitution C6-C10 arylene. In the embodiment, L1D is independently R1D-substitution C6 -C10 arylene. In the embodiment, L1D is independently unsubstituted C6-C10 arylene. It is R1D-substituted or unsubstituted phenylene. In the embodiment, L1D is independently R1D-substituted or unsubstituted phenylene. In this embodiment, L1D is independently R1D-substituted phenylene. In this embodiment, L1D is independently an unsubstituted phenylene. In this embodiment, L1D is independently R It is a 1D-substituted or unsubstituted biphenylene. In the embodiment, L1D is independently R1D - It is a substituted biphenylene. In the embodiment, L1D is independently an unsubstituted biphenylene. In the embodiment, L1D is independently R1D-substituted or unsubstituted naphthylene. In the embodiment, L1D is independently R1D-substituted naphthylene. It is independently an unsubstituted naphthylene.

[0212] In the embodiment, L1D is independently a substituted or unsubstituted heteroarylene. Morphologically, L1D is independently a substituted heteroarylene. In the embodiment, L1D is , independently, is an unsubstituted heteroarylene. In the embodiment, L1D is independently substituted or unsubstituted heteroarylenes (e.g., 5-12 member, 5-10 member, 5-9 member, or 5 (~6 members). In this embodiment, L1D is independently a substituted heteroarylene (e.g., (5-12 members, 5-10 members, 5-9 members, or 5-6 members). In this embodiment, L1D is Independently, unsubstituted heteroarylenes (e.g., 5-12 member, 5-10 member, 5-9 member, and (5-6 members). In this embodiment, L1D is independently substituted or non-substituted 5-12 member It is a teloarrine. In the embodiment, L1D is independently a substituted 5-12 member heteroary It is a ren. In the embodiment, L1D is independently an unsubstituted 5- to 12-membered heteroarylene. In the embodiment, L1D is independently a substituted or unsubstituted 5-10 member heteroarylene. Yes. In the embodiment, L1D is independently a substituted 5- to 10-membered heteroarylene. Morphologically, L1D is independently an unsubstituted 5- to 10-membered heteroarylene. In the embodiment, L1D is independently a substituted or unsubstituted 5- to 9-membered heteroarylene. In the embodiment, L1D is independently a substituted 5- to 9-membered heteroarylene. In the embodiment, L1D is independently It is an unsubstituted 5-9 member heteroarylene. In the embodiment, L1D is independently placed It is a substituted or unsubstituted 5-6 member heteroarylene. In the embodiment, L1D is independently placed It is a substituted 5-6 member heteroarylene. In the embodiment, L1D is independently an unsubstituted 5-6 member. It is a heteroarylene.

[0213] R1D is independently a substituted or unsubstituted alkyl group, or a substituted or unsubstituted heteroalkyl group. substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted Alternatively, it may be an unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0214] In the embodiment, L1E is independently bonded, substituted, or unsubstituted 2-10 member heteroalkyl groups. It is len, or -NHC(O)-. In the embodiment, L1E is independently a bond. In this embodiment, L1E is independently -NHC(O)-.

[0215] In the embodiment, L1E is independently a substituted or unsubstituted heteroalkylene. In this state, L1E is independently a substituted or unsubstituted 2- to 10-membered heteroalkylene. Morphologically, L1E is independently a substituted 2- to 10-membered heteroalkylene. In the embodiment, L1E is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L1E is They are independently substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L1E is Independently, they are substituted 2- to 8-membered heteroalkylenes. In the embodiment, L1E is independently non It is a substituted 2- to 8-membered heteroalkylene. In the embodiment, L1E is independently substituted or non-substituted. It is a substituted 5-8 member heteroalkylene. In the embodiment, L1E is independently a substituted 5-8 member It is a heteroalkylene. In the embodiment, L1E is independently an unsubstituted 5-8 member heteroalkylene. It is Kiren.

[0216] In the embodiment, L1E is independently R1E-substituted or unsubstituted heteroalkylene. In the embodiment, L1E is independently R1E-substituted or unsubstituted 2-10 member heteroalkyl It is Len. In the embodiment, L1E is independently R1E-substituted 2-10 member heteroalkyl In this embodiment, L1E is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L1E is independently R1E-substituted or unsubstituted 2-8 member heteroalkylates. In this embodiment, L1E is independently R1E-substituted 2- to 8-membered heteroalkylene. Yes. In the embodiment, L1E is independently an unsubstituted 2- to 8-membered heteroalkylene. Morphologically, L1E is independently an R1E-substituted or unsubstituted 5- to 8-membered heteroalkylene. In the embodiment, L1E is independently an R1E-substituted 5- to 8-membered heteroalkylene. In this embodiment, L1E is independently an unsubstituted 5- to 8-membered heteroalkylene.

[0217] R1E is independently a substituted or unsubstituted alkyl group, or a substituted or unsubstituted heteroalkyl group. substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted Alternatively, it may be an unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0218] In the embodiment, L1C is independently R1C-substituted or unsubstituted C1-C7 alkylene. , or R1C-substituted or unsubstituted 5-8 member heteroalkylenes, and L1D is independently And, bond, R1D-substituted or unsubstituted C1-C7 alkylene, or R1D-substituted The unsubstituted 5-8 member heteroalkylenes are L1E, which can independently bind, and R1E-substituted. Alternatively, it may be an unsubstituted 5- to 8-membered heteroalkylene, or -NHC(O)-. In the embodiment, L1C is independently an R1C-substituted or unsubstituted C1-C7 alkylene. In the embodiment, L1C is independently R1C-substituted or unsubstituted 5-8 member heteroalkyl It is a lens. In the embodiment, L1D is independent and coupled. In the embodiment, L1D is independent In this embodiment, it is an R1D-substituted or unsubstituted C1-C7 alkylene. These are independently bonded. In the embodiment, L1E is independently R1E-substituted or unsubstituted. It is a 5- to 8-membered heteroalkylene. In the embodiment, L1E is independently -NHC(O)- That is the case.

[0219] In this embodiment, R1C is independently oxo, or -L8C-L2C-R8C. In the embodiment, R1C is independently an oxo. In the embodiment, R1C is independently - The sequence is L8C-L2C-R8C. L8C is independently linked, substituted, or unsubstituted C1-C. It is a 6-alkylene, or a substituted or unsubstituted 2-6 member heteroalkylene. L8C is German In this structure, a bonded, substituted, or unsubstituted C1-C6 alkylene, or a substituted or unsubstituted 2 It is a 6-membered heteroalkylene. L2C is independently a bound or unsubstituted alkylene. R8C is independently hydrogen, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted group. It is heteroalkyl.

[0220] In this embodiment, R1D is independently oxo, or -L8D-L2D-R8D. In the embodiment, R1D is independently an oxo. In the embodiment, R1D is independently - The combination is L8D-L2D-R8D. L8D is independently linked, substituted, or unsubstituted C1-C. It is a 6-alkylene, or a substituted or unsubstituted 2-6 member heteroalkylene. L8D is German In this structure, a bonded, substituted, or unsubstituted C1-C6 alkylene, or a substituted or unsubstituted 2 It is a 6-membered heteroalkylene. L2D is independently a bound or unsubstituted alkylene. R8D is independently hydrogen, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyl. It is heteroalkyl.

[0221] In this embodiment, R1E is independently oxo, or -L8E-L2E-R8E. In the embodiment, R1E is independently an oxo. In the embodiment, R1E is independently - The order is L8E-L2E-R8E. L8E is independently linked, substituted, or unsubstituted C1-C. It is a 6-alkylene, or a substituted or unsubstituted 2-6 member heteroalkylene. L8E is German In this structure, a bonded, substituted, or unsubstituted C1-C6 alkylene, or a substituted or unsubstituted 2 It is a 6-membered heteroalkylene. L2E is independently a bound or unsubstituted alkylene. R8E is independently hydrogen, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyl group. It is heteroalkyl.

[0222] In this embodiment, the half-life extension motif has the following structure [ka] L8A independently binds, substituted or unsubstituted alkylenes, or substituted or unsubstituted hematophores. It is a teloalkylene. L2A is independently a bound or unsubstituted alkylene. L1 A, L1B, L1C, L1D, L1E, L2C, L8C, and R8C are as described above. That is the case.

[0223] In this embodiment, the half-life extension motif has the following structure [ka] L1A, L1B, L1C, L1D, L1E, L2A, L2D, L8A, L8D, and R 8D is as described above.

[0224] In this embodiment, the half-life extension motif has the following structure [ka] L1A, L1B, L1C, L1D, L1E, L2A, L2E, L8A, L8E, and R 8E is as described above.

[0225] In this embodiment, the half-life extension motif has the following structure [ka] L1A, L1B, L1C, L1D, L1E, L2A, L2C, L2D, L8A, L8C, L8D, R8C, and R8D are as described above.

[0226] In this embodiment, the half-life extension motif has the following structure [ka] L1A, L1B, L1C, L1D, L1E, L2A, L2D, L2E, L8A, L8D, L8E, R8D, and R8E are as described above.

[0227] In this embodiment, the half-life extension motif has the following structure [ka] L1A, L1B, L1C, L1D, L1E, L2A, L2C, L2E, L8A, L8C, L8E, R8C, and R8E are as described above.

[0228] In this embodiment, the half-life extension motif has the following structure [ka] L1A, L1B, L1C, L1D, L1E, L2A, L2C, L2D, L2E, L8A, L8C, L8D, L2E, R8C, R8D, and R8E are as described above.

[0229] In the embodiment, L8A is independent and coupled. In the embodiment, L8A is independent and placed It is a substituted or unsubstituted alkylene, or a substituted or unsubstituted heteroalkylene. In terms of form, L8A is independently a substituted or unsubstituted alkylene. In the embodiment, L8 A is independently a substituted or unsubstituted C1-C10 alkylene, or a substituted or unsubstituted C1-C10 alkylene. It is a 2- to 10-membered heteroalkylene. In the embodiment, L8A is independently substituted or absent. It is a substituted C1-C10 alkylene. In the embodiment, L8A is independently a substituted C1-C10 alkylene. It is an alkylene. In the embodiment, L8A is independently an unsubstituted C1-C10 alkylene. Yes. In the embodiment, L8A is independently a substituted or unsubstituted C1-C8 alkylene. In the embodiment, L8A is independently a substituted C1-C8 alkylene. In the embodiment, L8A is independently an unsubstituted C1-C8 alkylene. In the embodiment, L8A is independently And it is a substituted or unsubstituted C3-C8 alkylene. In the embodiment, L8A is independently It is a substituted C3-C8 alkylene. In the embodiment, L8A is independently an unsubstituted C3-C8 alkylene. It is an alkylene. In the embodiment, L8A is independently a substituted or unsubstituted C3-C7 alkylene. It is a kylene. In the embodiment, L8A is independently a substituted C3-C7 alkylene. In the application form, L8A is independently an unsubstituted C3-C7 alkylene.

[0230] In the embodiment, L8A is independently R8A-substituted or unsubstituted alkylene. Morphologically, L8A is independently either R8A-substituted or unsubstituted C1-C10 alkylene. In this embodiment, L8A is independently R8A-substituted C1-C10 alkylene. In its morphology, L8A is independently an unsubstituted C1-C10 alkylene. In the embodiment, L 8A is independently R8A-substituted C1-C8 alkylene. In the embodiment, L8A is independently In this embodiment, R8A is a substituted C1-C8 alkylene. It is an unsubstituted C1-C8 alkylene. In the embodiment, L8A is independently R8A-substituted. Or it is an unsubstituted C3-C8 alkylene. In the embodiment, L8A is independently R8A- It is a substituted C3-C8 alkylene. In the embodiment, L8A is independently an unsubstituted C3-C8 alkylene. It is ruquilen. In the embodiment, L8A is independently R8A-substituted or unsubstituted C3-C 7 is an alkylene. In the embodiment, L8A is independently R8A-substituted C3-C7 alkyl It is a len. In the embodiment, L8A is independently an unsubstituted C3-C7 alkylene.

[0231] In the embodiment, L8A is independently a substituted or unsubstituted heteroalkylene. In this state, L8A is independently a substituted or unsubstituted 2- to 10-membered heteroalkylene. Morphologically, L8A is independently a substituted 2- to 10-membered heteroalkylene. In the embodiment, L8A is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L8A is They are independently substituted or unsubstituted 2- to 8-membered heteroalkylenes. In the embodiment, L8A is Independently, they are substituted 2- to 8-membered heteroalkylenes. In the embodiment, L8A is independently non It is a substituted 2- to 8-membered heteroalkylene. In the embodiment, L8A is independently substituted or non-substituted. It is a substituted 5- to 8-membered heteroalkylene. In the embodiment, L8A is independently a substituted 5- to 8-membered heteroalkylene. It is a heteroalkylene. In the embodiment, L8A is independently an unsubstituted 5- to 8-membered heteroalkylene. It is Kiren.

[0232] In the embodiment, L8A is independently R8A-substituted or unsubstituted heteroalkylene. In the embodiment, L8A is independently R8A-substituted or unsubstituted 2-10 member heteroalkyl It is Ren. In the embodiment, L8A is independently R8A-substituted 2-10 member heteroalkyl In this embodiment, L8A is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L8A is independently R8A-substituted or unsubstituted 2- to 8-membered heteroalkylates. In this embodiment, L8A is independently R8A-substituted 2- to 8-membered heteroalkylene. Yes. In the embodiment, L8A is independently an unsubstituted 2- to 8-membered heteroalkylene. Morphologically, R8A-substituted or unsubstituted 5- to 8-membered heteroalkylenes. In embodiments, L8A These are independently R8A-substituted 5- to 8-membered heteroalkylenes. In the embodiment, L8A is independently In short, it is an unsubstituted 5- to 8-membered heteroalkylene.

[0233] In the embodiment, L2A is independently an unsubstituted C2-C24 alkylene. In this embodiment, L2A is an unsubstituted C2-C22 alkylene. Independently, it is an unsubstituted C5-C22 alkylene. In the embodiment, L2A is independently, non It is a substituted C10-C22 alkylene. In the embodiment, L2A is independently an unsubstituted C12 -C22 alkylene. In the embodiment, L2A is independently unsubstituted C10-C20 It is a lukilen. In the embodiment, L2A is independently an unsubstituted C12-C20 alkylene. Yes. In the embodiment, L2A is independently an unsubstituted C10-C18 alkylene. In its morphology, L2A is independently an unsubstituted C12-C18 alkylene. In an embodiment, L2A is independently an unsubstituted C10-C16 alkylene. In the embodiment, L2A is independently In this embodiment, L2A is an unsubstituted C12-C16 alkylene. It is a substituted C14-C16 alkylene. In the embodiment, L2A is independently an unsubstituted C14 -C15 alkylene. In the embodiment, L2A is independently an unsubstituted C14 alkylene. In this embodiment, L2A is independently an unsubstituted C15 alkylene. L2A is independently an unsubstituted C16 alkylene.

[0234] In this embodiment, L2A is independently an unsubstituted, unbranched C2-C24 alkylene. In its morphology, L2A is independently an unsubstituted, unbranched C2-C22 alkylene. In this embodiment, L2A is independently an unsubstituted, unbranched C5-C22 alkylene. 2A is independently an unsubstituted, unbranched C10-C22 alkylene. In the embodiment, L2A Independently, it is an unsubstituted, unbranched C12-C22 alkylene. In the embodiment, L2A is independent In this embodiment, it is an unsubstituted, unbranched C10-C20 alkylene. It is an unsubstituted, unbranched C12-C20 alkylene. In the embodiment, L2A is independently It is an unsubstituted, unbranched C10-C18 alkylene. In the embodiment, L2A is independently, non-positioned. It is a non-substituted non-branched C12-C18 alkylene. In the embodiment, L2A is independently a non-substituted non It is a branched C10-C16 alkylene. In the embodiment, L2A is independently unsubstituted and unbranched. It is a C12-C16 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched C1 It is a 4-C16 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched C14- It is C15 alkylene. In the embodiment, L2A is independently unsubstituted unbranched C14 alkylene. It is a cellulose compound. In the embodiment, L2A is independently an unsubstituted, unbranched C15 alkylene. In this embodiment, L2A is independently an unsubstituted, unbranched C16 alkylene.

[0235] In this embodiment, L2A is independently an unsubstituted, unbranched saturated C2-C24 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched saturated C2-C22 alkylene. In the application form, L2A is independently an unsubstituted, unbranched saturated C5-C22 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C10-C22 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C12-C22 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C10-C20 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C12-C20 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C10-C18 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C12-C18 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C10-C16 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C12-C16 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C14-C16 alkylene. Morphologically, L2A is independently an unsubstituted, unbranched saturated C14-C15 alkylene. In its morphology, L2A is independently an unsubstituted, unbranched saturated C14 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched saturated C15 alkylene. In the embodiment, L2A These are independently unsubstituted, unbranched, saturated C16 alkylenes.

[0236] In this embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C2-C24 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C2-C22 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C5-C22 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C10-C22 alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C12-C22 alkylene. Yes. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C10-C20 alkylene. In this embodiment, L2A is independently an unsubstituted, unbranched saturated C12-C20 alkylene. In this embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C10-C18 alkylate. In this embodiment, L2A independently provides an unsubstituted, unbranched, unsaturated C12-C18 alkyl group. In this embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C10-C16 aluminum alloy. It is a chelene. In the embodiment, L2A is independently an unsubstituted, unbranched saturated C12-C16 aluminum alloy. It is a chelene. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C14-C16 a It is ruquilen. In the embodiment, L2A is independently unsubstituted unbranched unsaturated C14-C15 It is an alkylene. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C14 alkylene. It is a len. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C15 alkylene. Yes. In the embodiment, L2A is independently an unsubstituted, unbranched, unsaturated C16 alkylene. In this embodiment, L8A is independently a bond, and L2A is independently a non-substituted C2-C22 It is alkylene.

[0237] In this embodiment, L2A is independently a bond, and L8A is independently a non-substituted C2-C2 It is a 2-alkylene.

[0238] In the embodiment, L8A is independently an unsubstituted C2-C24 alkylene. In this embodiment, L8A is independently an unsubstituted C2-C22 alkylene. Independently, it is an unsubstituted C5-C22 alkylene. In the embodiment, L8A is independently, non It is a substituted C10-C22 alkylene. In the embodiment, L8A is independently an unsubstituted C12 -C22 alkylene. In the embodiment, L8A is independently unsubstituted C10-C20 It is a lukilen. In the embodiment, L8A is independently an unsubstituted C12-C20 alkylene. Yes. In the embodiment, L8A is independently an unsubstituted C10-C18 alkylene. In its morphology, L8A is independently an unsubstituted C12-C18 alkylene. In its embodiment, L8A is independently an unsubstituted C10-C16 alkylene. In the embodiment, L8A is independently In this embodiment, L8A is independently a non-substituted C12-C16 alkylene. It is a substituted C14-C16 alkylene. In the embodiment, L8A is independently an unsubstituted C14 -C15 alkylene. In the embodiment, L8A is independently an unsubstituted C14 alkylene. In this embodiment, L8A is independently an unsubstituted C15 alkylene. L8A is independently an unsubstituted C16 alkylene.

[0239] In this embodiment, L8A is independently an unsubstituted, unbranched C2-C24 alkylene. In its morphology, L8A is independently an unsubstituted, unbranched C2-C22 alkylene. In this embodiment, L8A is independently an unsubstituted, unbranched C5-C22 alkylene. 8A is independently an unsubstituted, unbranched C10-C22 alkylene. In the embodiment, L8A It is independently an unsubstituted, unbranched C12-C22 alkylene. In the embodiment, L8A is independently In this embodiment, it is an unsubstituted, unbranched C10-C20 alkylene. It is an unsubstituted, unbranched C12-C20 alkylene. In the embodiment, L8A is independently It is an unsubstituted, unbranched C10-C18 alkylene. In the embodiment, L8A is independently, non-positioned. It is a non-substitutable non-branched C12-C18 alkylene. In the embodiment, L8A is independently a non-substitutable non It is a branched C10-C16 alkylene. In the embodiment, L8A is independently unsubstituted and unbranched. It is a C12-C16 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched C1 It is a 4-C16 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched C14- It is C15 alkylene. In the embodiment, L8A is independently unsubstituted unbranched C14 alkylene. It is a cellulose. In the embodiment, L8A is independently an unsubstituted, unbranched C15 alkylene. In this embodiment, L8A is independently an unsubstituted, unbranched C16 alkylene.

[0240] In this embodiment, L8A is independently an unsubstituted, unbranched saturated C2-C24 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched saturated C2-C22 alkylene. In the application form, L8A is independently an unsubstituted, unbranched saturated C5-C22 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C10-C22 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C12-C22 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C10-C20 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C12-C20 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C10-C18 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C12-C18 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C10-C16 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C12-C16 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C14-C16 alkylene. Morphologically, L8A is independently an unsubstituted, unbranched saturated C14-C15 alkylene. In its morphology, L8A is independently an unsubstituted, unbranched saturated C14 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched saturated C15 alkylene. In the embodiment, L8A These are independently unsubstituted, unbranched, saturated C16 alkylenes.

[0241] In this embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C2-C24 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C2-C22 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C5-C22 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C10-C22 alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C12-C22 alkylene. Yes. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C10-C20 alkylene. In this embodiment, L8A is independently an unsubstituted, unbranched saturated C12-C20 alkylene. In this embodiment, L8A independently provides an unsubstituted, unbranched, unsaturated C10-C18 alkylate. In this embodiment, L8A independently provides unsubstituted, unbranched, unsaturated C12-C18 alkyl It is a len. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C10-C16 aldehyde. It is a chelene. In the embodiment, L8A is independently an unsubstituted, unbranched saturated C12-C16 aluminum alloy. It is a chelene. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C14-C16 a It is ruquilen. In the embodiment, L8A is independently unsubstituted unbranched unsaturated C14-C15 It is an alkylene. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C14 alkylene. It is a len. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C15 alkylene. Yes. In the embodiment, L8A is independently an unsubstituted, unbranched, unsaturated C16 alkylene.

[0242] In this embodiment, R1C is independently -NHC(O)-L2C-R8C, and L2C is Independently, bonded or unsubstituted C2-C22 alkylenes, and R8C independently, hydrogen It is a C1-C3 alkyl group, or a -COOH group. In the embodiment, R1C is independently - It is NHC(O)-L2C-R8C. In the embodiment, L2C is independent, coupled, or It is an unsubstituted C2-C22 alkylene. In the embodiment, L2C is independently a bond. In the embodiment, L2C is independently an unsubstituted C2-C22 alkylene. R8C is independently hydrogen, C1-C3 alkyl, or -COOH. In embodiments In this embodiment, R8C is independently hydrogen. In this embodiment, R8C is independently C1-C3 aluminum It is a kill. In the embodiment, R8C is independently -COOH.

[0243] In this embodiment, R1C is independently -NHC(O)-L2C-R8C, and L2C is Independently, it is a bond, and R8C is independently a C1-C3 alkyl. In the embodiment, R1C is independently -NHC(O)-CH3. In the embodiment, R1C is independently It is -NHC(O)-CH2CH3. In the embodiment, R1C is independently -NHC(O )-CH(CH3)2. In the embodiment, R1C is independently -NHC(O)-CH It's 2CH2CH3.

[0244] In this embodiment, R1C is independently -NHC(O)-L2C-R8C, and L2C is Independently, it is an unsubstituted C10-C22 alkylene, and R8C is independently -COOH. In this embodiment, R1C is independently -NHC(O)-L2C-COOH.

[0245] In the embodiment, L2C is independently an unsubstituted, unbranched C2-C24 alkylene. In its morphology, L2C is independently an unsubstituted, unbranched C2-C22 alkylene. In this embodiment, L2C is independently an unsubstituted, unbranched C5-C22 alkylene. 2C is independently an unsubstituted, unbranched C10-C22 alkylene. In the embodiment, L2C Independently, L2C is an unsubstituted, unbranched C12-C22 alkylene. In the embodiment, L2C is independent In this embodiment, it is an unsubstituted, unbranched C10-C20 alkylene. It is an unsubstituted, unbranched C12-C20 alkylene. In the embodiment, L2C is independently It is an unsubstituted, unbranched C10-C18 alkylene. In the embodiment, L2C is independently, non-positioned. It is a non-substituted non-branched C12-C18 alkylene. In the embodiment, L2C is independently a non-substituted non It is a branched C10-C16 alkylene. In the embodiment, L2C is independently unsubstituted and unbranched. It is a C12-C16 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched C1 It is a 4-C16 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched C14- It is C15 alkylene. In the embodiment, L2C is independently unsubstituted unbranched C14 alkylene. It is a cellulose compound. In the embodiment, L2C is independently an unsubstituted, unbranched C15 alkylene. In this embodiment, L2C is independently an unsubstituted, unbranched C16 alkylene.

[0246] In the embodiment, L2C is independently an unsubstituted, unbranched saturated C2-C24 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched saturated C2-C22 alkylene. In the application form, L2C is independently an unsubstituted, unbranched saturated C5-C22 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C10-C22 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C12-C22 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C10-C20 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C12-C20 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C10-C18 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C12-C18 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C10-C16 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C12-C16 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C14-C16 alkylene. Morphologically, L2C is independently an unsubstituted, unbranched saturated C14-C15 alkylene. In its morphology, L2C is independently an unsubstituted, unbranched saturated C14 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched saturated C15 alkylene. In the embodiment, L2C These are independently unsubstituted, unbranched, saturated C16 alkylenes.

[0247] In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C2-C24 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C2-C22 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C5-C22 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C10-C22 alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C12-C22 alkylene. Yes. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C10-C20 alkylene. In this embodiment, L2C is independently an unsubstituted, unbranched saturated C12-C20 alkylene. In this embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C10-C18 alkylate. In this embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C12-C18 alkyl group. In this embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C10-C16 alloy. It is chelene. In the embodiment, L2C is independently unsubstituted unbranched saturated C12-C16 aluminum It is a chelene. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C14-C16 It is ruquilen. In the embodiment, L2C is independently unsubstituted unbranched unsaturated C14-C15 It is an alkylene. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C14 alkylene. It is a len. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C15 alkylene. Yes. In the embodiment, L2C is independently an unsubstituted, unbranched, unsaturated C16 alkylene.

[0248] In this embodiment, R1D is independently -NHC(O)-L2D-R8D, and L2D is Independently, bonded or unsubstituted C2-C22 alkylenes, and R8D independently, hydrogen It is a C1-C3 alkyl or -COOH group. In the embodiment, R1D is independently - The formula is NHC(O)-L2D-R8D. In the embodiment, L2D is independent, combined, or It is an unsubstituted C2-C22 alkylene. In the embodiment, L2D is independently a bond. In the embodiment, L2D is independently an unsubstituted C2-C22 alkylene. L2D is independently hydrogen, C1-C3 alkyl, or -COOH. In embodiments In this embodiment, R8D is independently hydrogen. In this embodiment, L2D is independently C1-C3 aluminum It is a kill. In the embodiment, R8D is independently -COOH.

[0249] In this embodiment, R1D is independently -NHC(O)-L2D-R8D, and L2D is Independently, it is a bond, and R8D is independently a C1-C3 alkyl. In the embodiment, R1D is independently -NHC(O)-CH3. In the embodiment, R1D is independently -NHC(O)-CH2DH3. In the embodiment, R1D is independently -NHC(O )-CH(CH3)2. In the embodiment, R1D is independently -NHC(O)-CH It is 2DH2DH3.

[0250] In this embodiment, R1D is independently -NHC(O)-L2D-R8D, and L2D is Independently, it is an unsubstituted C10-C22 alkylene, and R8D is independently -COOH. In this embodiment, R1D is independently -NHC(O)-L2D-COOH.

[0251] In the embodiment, L2D is independently an unsubstituted, unbranched C2-C24 alkylene. In its morphology, L2D is independently an unsubstituted, unbranched C2-C22 alkylene. In this embodiment, L2D is independently an unsubstituted, unbranched C5-C22 alkylene. 2D is independently an unsubstituted, unbranched C10-C22 alkylene. In the embodiment, L2D Independently, it is an unsubstituted, unbranched C12-C22 alkylene. In the embodiment, L2D is independent In this embodiment, it is an unsubstituted, unbranched C10-C20 alkylene. It is an unsubstituted, unbranched C12-C20 alkylene. In the embodiment, L2D is independently It is an unsubstituted, unbranched C10-C18 alkylene. In the embodiment, L2D is independently, non-positioned. It is a non-substitutable non-branched C12-C18 alkylene. In the embodiment, L2D is independently a non-substitutable non It is a branched C10-C16 alkylene. In the embodiment, L2D is independently unsubstituted and unbranched. It is a C12-C16 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched C1 It is a 4-C16 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched C14- It is C15 alkylene. In the embodiment, L2D is independently unsubstituted unbranched C14 alkylene. It is a len. In the embodiment, L2D is independently an unsubstituted, unbranched C15 alkylene. In this embodiment, L2D is independently an unsubstituted, unbranched C16 alkylene.

[0252] In this embodiment, L2D is independently an unsubstituted, unbranched saturated C2-C24 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched saturated C2-C22 alkylene. In the application form, L2D is independently an unsubstituted, unbranched saturated C5-C22 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C10-C22 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C12-C22 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C10-C20 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C12-C20 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C10-C18 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C12-C18 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C10-C16 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C12-C16 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C14-C16 alkylene. Morphologically, L2D is independently an unsubstituted, unbranched saturated C14-C15 alkylene. In its morphology, L2D is independently an unsubstituted, unbranched saturated C14 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched saturated C15 alkylene. In the embodiment, L2D These are independently unsubstituted, unbranched, saturated C16 alkylenes.

[0253] In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C2-C24 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C2-C22 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C5-C22 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C10-C22 alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C12-C22 alkylene. Yes. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C10-C20 alkylene. In this embodiment, L2D is independently an unsubstituted, unbranched saturated C12-C20 alkylene. In this embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C10-C18 alkylate. In this embodiment, L2D independently provides an unsubstituted, unbranched, unsaturated C12-C18 alkyl group. In this embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C10-C16 alloy. It is chelene. In the embodiment, L2D is independently unsubstituted unbranched saturated C12-C16 aluminum It is a chelene. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C14-C16 It is ruquilen. In the embodiment, L2D is independently unsubstituted unbranched unsaturated C14-C15 It is an alkylene. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C14 alkylene. It is a len. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C15 alkylene. Yes. In the embodiment, L2D is independently an unsubstituted, unbranched, unsaturated C16 alkylene.

[0254] In this embodiment, R1E is independently -NHC(O)-L2E-R8E, and L2E is Independently, bonded or unsubstituted C2-C22 alkylenes, and R8E independently is hydrogen. It is a C1-C3 alkyl or -COOH group. In the embodiment, R1E is independently - It is NHC(O)-L2E-R8E. In the embodiment, L2E is independent, combined, or It is an unsubstituted C2-C22 alkylene. In the embodiment, L2E is independently a bond. In the embodiment, L2E is independently an unsubstituted C2-C22 alkylene. R8E is independently hydrogen, C1-C3 alkyl, or -COOH. In embodiments In this embodiment, R8E is independently hydrogen. In this embodiment, R8E is independently C1-C3 aluminum It is a kill. In the embodiment, R8E is independently -COOH.

[0255] In this embodiment, R1E is independently -NHC(O)-L2E-R8E, and L2E is Independently, it is a bond, and R8E is independently a C1-C3 alkyl. In the embodiment, R1E is independently -NHC(O)-CH3. In the embodiment, R1E is independently -NHC(O)-CH2EH3. In the embodiment, R1E is independently -NHC(O )-CH(CH3)2. In the embodiment, R1E is independently -NHC(O)-CH The formula is 2EH2EH3.

[0256] In this embodiment, R1E is independently -NHC(O)-L2E-R8E, and L2E is Independently, it is an unsubstituted C10-C22 alkylene, and R8E is independently -COOH. In this embodiment, R1E is independently -NHC(O)-L2E-COOH.

[0257] In the embodiment, L2E is independently an unsubstituted, unbranched C2-C24 alkylene. In its morphology, L2E is independently an unsubstituted, unbranched C2-C22 alkylene. In this embodiment, L2E is independently an unsubstituted, unbranched C5-C22 alkylene. 2E is independently an unsubstituted, unbranched C10-C22 alkylene. In the embodiment, L2E Independently, it is an unsubstituted, unbranched C12-C22 alkylene. In the embodiment, L2E is independent In this embodiment, it is an unsubstituted, unbranched C10-C20 alkylene. It is an unsubstituted, unbranched C12-C20 alkylene. In the embodiment, L2E is independently It is an unsubstituted, unbranched C10-C18 alkylene. In the embodiment, L2E is independently, non-positioned. It is a non-substitutable non-branched C12-C18 alkylene. In the embodiment, L2E is independently a non-substitutable non It is a branched C10-C16 alkylene. In the embodiment, L2E is independently unsubstituted and unbranched. It is a C12-C16 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched C1 It is a 4-C16 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched C14- It is C15 alkylene. In the embodiment, L2E is independently unsubstituted unbranched C14 alkylene. It is a len. In the embodiment, L2E is independently an unsubstituted, unbranched C15 alkylene. In this embodiment, L2E is independently an unsubstituted, unbranched C16 alkylene.

[0258] In the embodiment, L2E is independently an unsubstituted, unbranched saturated C2-C24 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched saturated C2-C22 alkylene. In the application configuration, L2E is independently an unsubstituted, unbranched saturated C5-C22 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C10-C22 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C12-C22 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C10-C20 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C12-C20 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C10-C18 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C12-C18 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C10-C16 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C12-C16 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C14-C16 alkylene. Morphologically, L2E is independently an unsubstituted, unbranched saturated C14-C15 alkylene. In its morphology, L2E is independently an unsubstituted, unbranched saturated C14 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched saturated C15 alkylene. In the embodiment, L2E These are independently unsubstituted, unbranched, saturated C16 alkylenes.

[0259] In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C2-C24 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C2-C22 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C5-C22 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C10-C22 alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C12-C22 alkylene. Yes. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C10-C20 alkylene. In this embodiment, L2E is independently an unsubstituted, unbranched saturated C12-C20 alkylene. In this embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C10-C18 alkylate. In this embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C12-C18 alkyl group. In this embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C10-C16 alloy. It is chelene. In the embodiment, L2E is independently unsubstituted unbranched saturated C12-C16 aluminum It is a chelene. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C14-C16 a It is ruquilen. In the embodiment, L2E is independently unsubstituted unbranched unsaturated C14-C15 It is an alkylene. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C14 alkylene. It is a len. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C15 alkylene. Yes. In the embodiment, L2E is independently an unsubstituted, unbranched, unsaturated C16 alkylene.

[0260] In the embodiment, L1C is independently R1C-substituted or unsubstituted 5- to 8-membered heteroalkylates. L1D is independently bonded, or R1D-substituted or unsubstituted 5-8 member heterozygotes. It is an alkylene, and L1E is independently R1E-substituted or unsubstituted 5-8 member heteroal It is kylene, or -NHC(O)-. In the embodiment, each R1C, R1D, or R1 E is independently either oxo or -COOH.

[0261] In the embodiment, L1C is independently an unsubstituted 5- to 8-membered heteroalkylene. Embodiment Therefore, L1D is independently an oxo-substituted or unsubstituted 5- to 8-membered heteroalkylene. In the embodiment, L1E is independently R1E-substituted or unsubstituted 5- to 8-membered heteroalkylene And R1E is independently oxo or -COOH. In the embodiment, L1C is Independently, they are unsubstituted 5-8 member heteroalkylenes. In the embodiment, L1D is independently, It is a bond. In the embodiment, L1E is independently -NHC(O)-. In the embodiment -L1C-L1D-L1E- is, [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form.

[0262] In this embodiment, L1C is independently an R1C-substituted C2-C5 alkyl, and L1D is Independently, they are unsubstituted phenylene or unsubstituted biphenylene, and L1E is independently R1 E-substituted or unsubstituted 5- to 8-membered heteroalkylene or -NHC(O)-, R1 C is independently -NHC(O)-L2C-R8C, and L2C is independently bonded, and R8C is an unsubstituted C10-C22 alkylene, and R8C is independently an unsubstituted C1-C3 alkylene. It is -COOH, and R1E is oxo.

[0263] In the embodiment, L1C is independently R1C-substituted ethylene. D is independently an unsubstituted biphenylene. In the embodiment, L1E is independently -NHC (O)-. In the embodiment, R1C is independently -NHC(O)-L2C-R8. L2C is independently a bond, or R8C is independently an unsubstituted C1-C3 alkyl group. In this embodiment, R1C is independently -NHC(O)-CH3. Then, R1C is independently -NHC(O)-CH2CH3. In the embodiment, R1C Independently, is -NHC(O)-CH(CH3)2. In the embodiment, R1C is independently And it is -NHC(O)-CH2CH2CH3. In the embodiment, R1C is independently, - It is NHC(O)-L2C-COOH. In the embodiment, -L1C-L1D-L1E- is , [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form.

[0264] In the embodiment, L1C is independently R1C-substituted ethylene. D is independently an unsubstituted phenylene. In the embodiment, L1E is independently R1E-substituted It is a substituted or unsubstituted 5-8 member heteroalkylene. In the embodiment, L1E is independently O It is a xo-substituted or unsubstituted 5- to 8-membered heteroalkylene. In the embodiment, R1C is independent And it is -NHC(O)-L2C-R8, where L2C is independently a bond or R 8C is independently an unsubstituted C1-C3 alkyl. In the embodiment, R1C is independently It is -NHC(O)-CH3. In the embodiment, R1C is independently -NHC(O)-C It is H2CH3. In the embodiment, R1C is independently -NHC(O)-CH(CH3) 2. In the embodiment, R1C is independently -NHC(O)-CH2CH2CH3 In this embodiment, R1C is independently -NHC(O)-L2C-COOH. In terms of morphology, -L1C-L1D-L1E- is, [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form.

[0265] In the embodiment, L1C is independently R1C-substituted or unsubstituted ethylene, or n- Pentylene, L1D independently, bond, L1E independently, -NHC(O) - and R1C is independently -NHC(O)-L2C-R8C, and L2C is independently The bond is either an unsubstituted C10-C22 alkylene, and R8C is independently an unsubstituted C It is a 1-C3 alkyl group or a -COOH group.

[0266] In the embodiment, L1C is independently R1C-substituted n-pentylene. L1C is independently an unsubstituted n-pentylene. In the embodiment, L1D is independently It is a bond. In the embodiment, L1E is independently -NHC(O)-. In the embodiment R1C is independently -NHC(O)-L2C-R8, and L2C is independently bonded Yes, R8C is independently an unsubstituted C1-C3 alkyl. In the embodiment, R1C is independently Therefore, it is -NHC(O)-CH3. In the embodiment, R1C is independently -NHC( It is O)-CH2CH3. In the embodiment, R1C is independently -NHC(O)-CH( It is CH3)2. In the embodiment, R1C is independently -NHC(O)-CH2CH2C It is H3. In the embodiment, R1C is independently -NHC(O)-L2C-COOH In this embodiment, -L1C-L1D-L1E- are [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form.

[0267] In the embodiment, L1C is independently R1C-substituted ethylene. D is independently a bond. In this embodiment, L1E is independently -NHC(O)-. In this embodiment, R1C is independently -NHC(O)-L2C-R8, and L2C is independently In this embodiment, the bond is such that R8C is independently an unsubstituted C1-C3 alkyl group. In this embodiment, R1C is independently -NHC(O)-CH3. Therefore, it is -NHC(O)-CH2CH3. In the embodiment, R1C is independently -NHC It is (O)-CH(CH3)2. In the embodiment, R1C is independently -NHC(O)- It is CH2CH2CH3. In the embodiment, R1C is independently -NHC(O)-L2C -R8C is, L2C is independently an unsubstituted C10-C22 alkylene, and R8C is Independently, it is -COOH. In the embodiment, R1C is independently -NHC(O)-L2 It is C-COOH. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form.

[0268] In the embodiment, L1C is independently R1C-substituted or unsubstituted n-pentylene. L1D is independently an oxo-substituted or unsubstituted 5- to 8-membered heteroalkylene, and L1 E is independently -NHC(O)-, and R1C is independently -NHC(O)-L2C- R8C is a bonded or unsubstituted C10-C22 alkylene, and L2C is independently a bonded or unsubstituted C10-C22 alkylene. R8C is independently an unsubstituted C1-C3 alkyl group or a -COOH group.

[0269] In the embodiment, L1C is independently R1C-substituted n-pentylene. L1D is independently an oxo-substituted or unsubstituted 5- to 8-membered heteroalkylene. Morphologically, L1E is independently -NHC(O)-. In the embodiment, R1C is independently So, it's -NHC(O)-L2C-R8, where L2C is independent and bonded, and R8C is independent. In this embodiment, it is an unsubstituted C1-C3 alkyl group. In this embodiment, R1C is independently -NHC It is (O)-CH3. In the embodiment, R1C is independently -NHC(O)-CH2CH 3. In the embodiment, R1C is independently -NHC(O)-CH(CH3)2. In this embodiment, R1C is independently -NHC(O)-CH2CH2CH3. Morphologically, R1C is independently -NHC(O)-L2C-R8C, and L2C is independently Therefore, it is an unsubstituted C10-C22 alkylene, and R8C is independently an unsubstituted C1-C3 alkylene. It is a kill. In the embodiment, R1C is independently -NHC(O)-L2C-R8C L2C is independently an unsubstituted C10-C22 alkylene, and R8C is independently an unsubstituted C10-C22 alkylene. It is a methyl substitution. In the embodiment, R1C is independently -NHC(O)-L2C-R8C Yes, L2C is independently an unsubstituted C10-C22 alkylene, and R8C is independently, It is unsubstituted ethyl. In the embodiment, R1C is independently -NHC(O)-L2C-R8 C is, L2C is independently an unsubstituted C10-C22 alkylene, and R8C is independently And it is -COOH. In the embodiment, R1C is independently -NHC(O)-L2C-C It is OOH. In the embodiment, R1C is independently -NHC(O)-L2C-R8C L2C is independently an unsubstituted C10-C22 alkylene, and R8C is independently - It is COOH. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form.

[0270] In this embodiment, L1C is independently R1C-substituted methylene, and L1D is independently, This is a bond, where L1E is independently -NHC(O)- and R1C is independently -L8C- L2C-R8C, where L8C is independently an unsubstituted C1-C6 alkylene or oxo- The substituted 2-12 member heteroalkylene is L2C independently bonded, and R8C independently bonded. These are unsubstituted C1-C6 alkyl groups or oxo-substituted 2-12 member heteroalkyl groups.

[0271] In the embodiment, L1C is independently an R1C-substituted methylene group. D is independently a bond. In this embodiment, L1E is independently -NHC(O)-. In this embodiment, R1C is independently -L8C-L2C-R8C. L8C is independently an unsubstituted C1-C6 alkylene or an oxo-substituted 2-12 member heterogene. It is a lukilen. In the embodiment, L8C is independently an unsubstituted C1-C6 alkylene. In the embodiment, L8C is independently an oxo-substituted 2- to 12-membered heteroalkylene. In the embodiment, R8C is independently an unsubstituted C1-C6 alkyl. C is independently an oxo-substituted 2- to 12-membered heteroalkyl. In the embodiment, L8C is Independently, it is an unsubstituted C1-C6 alkylene, L2C is a bond, and R8C is independently It is an oxo-substituted 2- to 12-membered heteroalkyl group. In the embodiment, L8C is independently It is an unsubstituted C4 alkylene, L2C is a bond, and R8C is independently oxo-substituted. It is a 2- to 5-membered heteroalkyl group. In the embodiment, L8C is independently an unsubstituted C4 alkylate. L2C is a bond, R8C is independently an oxo-substitution, and C1-C2 It is an alkyl-substituted 2- to 12-membered heteroalkyl group. In the embodiment, L8C is independently non It is a substituted C1-C6 alkylene, L2C is a bond, and R8C is independently oxo- and C1-C15 alkyl-substituted 2-12 member heteroalkyl groups. In the embodiment, L8 C is independently an unsubstituted C4 alkylene, L2C is a bond, and R8C is independently These are oxo- and C14-C15 alkyl-substituted 2- to 12-membered heteroalkyl groups. In this state, L8C is independently an oxo-substituted 2-12 member heteroalkylene, and L2C is The bond is, and R8C is independently an oxo-substituted 2- to 12-membered heteroalkyl group. Morphologically, L8C is independently an oxo-substituted 2-12 member heteroalkylene, and L2C The bond is R8C, and R8C is independently oxo- and C1-C15 alkyl substituted 2-12 It is a heteroalkyl group. In the embodiment, L8C is independently an oxo-substituted 2- to 12-member heteroalkyl group. It is a teloalkylene, L2C is a bond, and R8C is independently oxo- and C1 It is a 4-C15 alkyl-substituted 2- to 12-membered heteroalkyl group. In the embodiment, -L1C-L 1D-L1E- is, [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form. In this embodiment, -L1C-L1D-L1E- is [ka] It can form.

[0272] In this embodiment, L1 is [ka] [ka] [ka] That is the case.

[0273] In this embodiment, L1 is independently [ka] In this embodiment, L1 is independently [ka] In this embodiment, L1 is independently [ka] In this embodiment, L1 is independently [ka] In this embodiment, L1 is independently [ka] In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] That is the case. In this embodiment, L1 is independently [ka] In this embodiment, L1 is independently [ka] That is the case.

[0274] In this embodiment, L1 is [ka] In this embodiment, L1 is [ka] In this embodiment, L1 is [ka] In this embodiment, L1 is [ka] In this embodiment, L1 is [ka] In this embodiment, L1 is [ka] In this embodiment, L1 is [ka] That is the case.

[0275] In this embodiment, HLEM is [ka] In this embodiment, HLEM is [ka] In this embodiment, HLEM is [ka] In this embodiment, HLEM is [ka] In this embodiment, HLEM is [ka] In this embodiment, HLEM is [ka] That is the case.

[0276] In the embodiment, the compound comprises 1 to 5 arbitrarily different half-life extension motifs. In this embodiment, the compound contains 1 to 4 arbitrarily different half-life extension motifs. The compound contains one to three arbitrarily different half-life extension motifs. In embodiments, the compound , comprising 1-2 arbitrarily different half-life extension motifs. In embodiments, the compound contains 2-5 It contains different half-life extension motifs. In embodiments, the compound contains 2 to 4 different half-life extension motifs. Includes half-life extension motifs. In embodiments, the compound includes 2-3 different half-life extension motifs. This includes. In embodiments, the compound includes two different half-life extension motifs. The compound contains only one half-life extension motif.

[0277] In this embodiment, the incorporated motif independently has the following structure [ka]

[0278] L3 and L4 independently bond -N(R23)-, -O-, -S-, -C(O)- , -N(R23)C(O)-, -C(O)N(R24)-, -N(R23)C(O)N( R24)-, -C(O)O-, -OC(O)-, -N(R23)C(O)O-, -OC( O)N(R24)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O) (R25)-O-, -OP(S)(R25)-O-, -OP(O)(NR23R24 )-N-, -OP(S)(NR23R24)-N-, -OP(O)(NR23R24 )-O-, -OP(S)(NR23R24)-O-, -P(O)(NR23R24)- N-, -P(S)(NR23R24)-N-, -P(O)(NR23R24)-O-, - P(S)(NR23R24)-O-, -SS-, substituted or unsubstituted alkylene, substituted Or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or Unsubstituted heterocycloalkyl, substituted or unsubstituted arylene, or substituted or unsubstituted It is a heteroarylene. Each of R23, R24, and R25 independently contains hydrogen, or It is an unsubstituted C1-C10 alkyl group.

[0279] L5 is -L5A-L5B-L5C-L5D-L5E- and L6 is -L6A-L 6B-L6C-L6D-L6E-. L5A, L5B, L5C, L5D, L5E, L 6A, L6B, L6C, L6D, and L6E are independently bonded, -NH-, -O-, - S-, -C(O)-, -NHC(O)-, -NHC(O)NH-, -C(O)O-, -O C(O)-, -C(O)NH-, substituted or unsubstituted alkylenes, substituted or unsubstituted helium Teloalkylenes, substituted or unsubstituted cycloalkylenes, substituted or unsubstituted heteroalkylenes Roalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene It's Ren.

[0280] R1 and R2 are independently unsubstituted C1-C25 alkyl groups, and R1 and R2 At least one of these is an unsubstituted C9-C19 alkyl. In the embodiment, R1 and R2 is independently an unsubstituted C1-C20 alkyl, and at least one of R1 and R2 Another type is the unsubstituted C9-C19 alkyl group.

[0281] R3 is hydrogen, -NH2, -OH, -SH, -C(O)H, -C(O)NH2, -NH C(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 It is an unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0282] t is an integer between 1 and 5.

[0283] In the embodiment, t is 1. In the embodiment, t is 2. In the embodiment, t is , 3. In the embodiment, t is 4. In the embodiment, t is 5.

[0284] In the embodiment, one L3 is bonded to the 3' carbon of the oligonucleotide. One L3 is the 3' nitrogen of the oligonucleotide (for example, the 3' nitrogen of the morpholino moiety). It binds to the oligonucleotide. In this embodiment, one L3 is bound to the 5' carbon of the oligonucleotide. In the embodiment, one L3 is the 6' carbon of the oligonucleotide (for example, morphol It bonds to the 6' carbon of the part. In this embodiment, one L3 is 2 of the oligonucleotide. 'Bonds with carbon, and in the embodiment, one L3 bonds with the nucleic acid base of the oligonucleotide. ru.

[0285] In this embodiment, one L3 is bonded to the 3' carbon of the oligonucleotide at its 3' end. In the embodiment, one L3 has the 3' nitrogen of the oligonucleotide at its 3' end (e.g., mole It binds to the 3' nitrogen of the folino portion. In one embodiment, one L3 is oligo at the 5' end. It binds to the 5' carbon of the nucleotide. In this embodiment, one L3 is oligonucleotide at the 5' end. It bonds to the 6' carbon of the creotide (for example, the 6' carbon of the morpholino moiety).

[0286] In this embodiment, one L3 has a double-stranded oligonucleotide at either of its 3' ends. It bonds to the 3' carbon. In the embodiment, one L3 is doubled at the 3' end of its antisense chain. It bonds to the 3' carbon of the main chain oligonucleotide. In the embodiment, one L3 is its chise The 3' end of the lance chain binds to the 3' carbon of the double-stranded oligonucleotide.

[0287] In this embodiment, one L3 has a double-stranded oligonucleotide at either of its 3' ends. It binds to the 3' nitrogen (for example, the 3' nitrogen of the morpholino moiety). In the embodiment, one L 3 is the 3' nitrogen of the double-stranded oligonucleotide at the 3' end of its antisense chain (for example, It binds to the 3' nitrogen of the morpholino moiety. In one embodiment, one L3 is its sense chain At the 3' end of the double-stranded oligonucleotide (for example, the 3' nitrogen of the morpholino portion) It combines with (a prime element).

[0288] In this embodiment, one L3 has a double-stranded oligonucleotide at either of its 5' ends. It bonds to the 5' carbon. In the embodiment, one L3 is doubled at the 5' end of its antisense chain. It binds to the 5' carbon of the main-chain oligonucleotide. In the embodiment, one L3 is its stem It binds to the 5' carbon of the double-stranded oligonucleotide at the 5' end of the s chain.

[0289] In this embodiment, one L3 has a double-stranded oligonucleotide at either of its 5' ends. It bonds to the 6' carbon (for example, the 6' carbon of the morpholino moiety). In one embodiment, L3 is the 6' carbon of the double-stranded oligonucleotide at the 5' end of its antisense chain (for example) , bonded to the 6' carbon of the morpholino moiety. In the embodiment, one L3 is its sense The 6' carbon of a double-stranded oligonucleotide at the 5' end of the chain (for example, the 6' carbon of the morpholino portion) It bonds with carbon.

[0290] In this embodiment, one L3 is bonded to the 2' carbon of the double-stranded oligonucleotide. Morphologically, one L3 has the 2' carbon of a double-stranded oligonucleotide at either of its 3' ends. It binds to the element. In one embodiment, one L3 has a double strand at the 3' end of its antisense strand. It binds to the 2' carbon of the ligonucleotide. In embodiments, one L3 is attached to its cysnes chain. It bonds to the 2' carbon of the double-stranded oligonucleotide at its 3' end. In the embodiment, one L 3 binds to the 2' carbon of the double-stranded oligonucleotide at one of its 5' ends. Morphologically, one L3 has a double-stranded oligonucleotide at the 5' end of its antisense strand. It bonds to the 2' carbon. In the embodiment, one L3 is double-stranded at the 5' end of its sense chain. It bonds to the 2' carbon of the ligonucleotide.

[0291] In this embodiment, one L3 binds to a nucleic acid base of a double-stranded oligonucleotide. Morphologically, one L3 molecule has a double-stranded oligonucleotide nucleic acid salt at either of its 3' ends. It binds to the group. In one embodiment, one L3 is double-stranded at the 3' end of its antisense chain. It binds to the nucleic acid base of a ligonucleotide. In the embodiment, one L3 is of its sense strand It binds to the nucleic acid base of the double-stranded oligonucleotide at its 3' end. In this embodiment, one L3 It binds to a nucleic acid base of a double-stranded oligonucleotide at one of its 5' ends. In this state, one L3 is the nucleus of the double-stranded oligonucleotide at the 5' end of its antisense strand. It binds to acids and bases. In one embodiment, one L3 is double-stranded at the 5' end of its sense strand. It binds to the nucleic acid base of a nucleotide.

[0292] In this embodiment, one L3 is bonded to the 3' carbon of a single-stranded oligonucleotide at its 3' end. In this embodiment, one L3 is at the 3' end of the single-stranded oligonucleotide. It binds to the 3' nitrogen of a gonucleotide (for example, the 3' nitrogen of the morpholino moiety).

[0293] In this embodiment, one L3 is bonded to the 5' carbon of a single-stranded oligonucleotide at its 5' end. do.

[0294] In this embodiment, one L3 is the 6' carbon of a single-stranded oligonucleotide at its 5' end (for example) Then, it bonds with the 6' carbon of the morpholino portion.

[0295] In this embodiment, one L3 is bonded to the 2' carbon of a single-stranded oligonucleotide. Morphologically, one L3 molecule is bonded to the 2' carbon of a single-stranded oligonucleotide at its 5' end. In this embodiment, one L3 is bonded to the 2' carbon of a single-stranded oligonucleotide at its 3' end. ru.

[0296] In this embodiment, one L3 binds to a nucleic acid base of a single-stranded oligonucleotide. Morphologically, one L3 molecule binds to a nucleic acid base of a single-stranded oligonucleotide at its 3' end. In this embodiment, one L3 binds to a nucleic acid base of a single-stranded oligonucleotide at its 5' end. ru.

[0297] In this embodiment, L3 is a bond, -N(R23)-, -O-, -S-, -C(O)-, - N(R23)C(O)-, -C(O)N(R24)-, -N(R23)C(O)N(R2 4)-, -C(O)O-, -OC(O)-, -N(R23)C(O)O-, -OC(O) N(R24)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25)-O-, -OP(S)(R25)-O-, -OP(O)(NR23R24)- N-, -OP(S)(NR23R24)-N-, -OP(O)(NR23R24)- O-, -OP(S)(NR23R24)-O-, -P(O)(NR23R24)-N- , -P(S)(NR23R24)-N-, -P(O)(NR23R24)-O-, -P( S)(NR23R24)-O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted alkylene k is an unsubstituted heteroalkylene, a substituted or unsubstituted cycloalkylene, or a substituted or unsubstituted cycloalkylene. Substituting heterocycloalkyls, substituted or unsubstituted arylenes, or substituted or unsubstituted he It is terrorarylene.

[0298] In the embodiment, L3 is a bond. In the embodiment, L3 is -N(R23)-. In the embodiment, L3 is -O- or -S-. In the embodiment, L3 is -C(O) -In this embodiment, L3 is -N(R23)C(O)- or -C(O)N(R2 4) - In this embodiment, L3 is -N(R23)C(O)N(R24)-. In the embodiment, L3 is -C(O)O- or -OC(O)-. 3 is -N(R23)C(O)O- or -OC(O)N(R24)-. Embodiment So, L3 is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R2 5)-O-, -OP(O)(NR23R24)-N-, or OP(O)(NR23 It is R24)-O-. In the embodiment, L3 is -P(O)(NR23R24)-N-. -P(S)(NR23R24)-N-, -P(O)(NR23R24)-O-, or - It is P(S)(NR23R24)-O-. In the embodiment, L3 is -SS-.

[0299] In the embodiment, L3 is independently a substituted or unsubstituted alkylene (e.g., C1-C23) These are C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the application form, L3 independently substitutes alkylenes (e.g., C1-C23, C1-C12, These are C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L3 These are independently unsubstituted alkylenes (e.g., C1-C23, C1-C12, C1-C8, C 1-C6, C1-C4, or C1-C2). In this embodiment, L3 is independently placed It is a substituted or unsubstituted C1-C23 alkylene. In the embodiment, L3 is independently a substituted C It is a 1-C23 alkylene. In the embodiment, L3 is independently an unsubstituted C1-C23 alkylene. It is a chylene. In the embodiment, L3 is independently a substituted or unsubstituted C1-C12 alkylene. In this embodiment, L3 is independently a substituted C1-C12 alkylene. In this embodiment, L3 is independently an unsubstituted C1-C12 alkylene. In this embodiment, L3 is Independently, it is a substituted or unsubstituted C1-C8 alkylene. In the embodiment, L3 is independently And it is a substituted C1-C8 alkylene. In the embodiment, L3 is independently an unsubstituted C1-C 8. Alkylene. In the embodiment, L3 is independently substituted or unsubstituted C1-C6 alkylene. It is a chylene. In the embodiment, L3 is independently a substituted C1-C6 alkylene. In its morphology, L3 is independently an unsubstituted C1-C6 alkylene. In the embodiment, L3 is Independently, it is a substituted or unsubstituted C1-C4 alkylene. In the embodiment, L3 is independently And it is a substituted C1-C4 alkylene. In the embodiment, L3 is independently an unsubstituted C1-C 4. Alkylene. In the embodiment, L3 is independently substituted or unsubstituted ethylene. In the embodiment, L3 is independently substituted ethylene. In the embodiment, L3 is independently , unsubstituted ethylene. In the embodiment, L3 is independently substituted or unsubstituted methylene. Yes. In the embodiment, L3 is independently a substituted methylene group. In the embodiment, L3 is independently And it is an unsubstituted methylene group.

[0300] In the embodiment, L3 is independently a substituted or unsubstituted heteroalkylene (e.g., 2-2 (3 members, 2-12 members, 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members) In the embodiment, L3 is independently a substituted heteroalkylene (e.g., 2-23 member, 2-1 The number of members is 2, 2-8, 2-6, 4-6, 2-3, or 4-5. L3 is independently an unsubstituted heteroalkylene (e.g., 2-23 member, 2-12 member, 2- (8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members). In this embodiment, L3 is Independently, they are substituted or unsubstituted 2- to 23-membered heteroalkylenes. In the embodiment, L3 is Independently, it is a substituted 2- to 23-membered heteroalkylene. In the embodiment, L3 is independently non It is a substituted 2- to 23-membered heteroalkylene. In the embodiment, L3 is independently substituted or non-substituted. It is a substituted 2- to 8-membered heteroalkylene. In the embodiment, L3 is independently a substituted 2- to 8-membered heteroalkylene. It is a teloalkylene. In the embodiment, L3 is independently an unsubstituted 2-8 member heteroalkylene. In this embodiment, L3 is independently a substituted or unsubstituted 2-6 member heteroalkylene. In this embodiment, L3 is independently a substituted 2- to 6-membered heteroalkylene. In this embodiment, L3 is independently an unsubstituted 2- to 6-membered heteroalkylene. These are independently substituted or unsubstituted 4-6 member heteroalkylenes. In the embodiment, L3 is Independently, it is a substituted 4-6 member heteroalkylene. In the embodiment, L3 is independently non-substituted. It is a substituted 4-6 member heteroalkylene. In the embodiment, L3 is independently substituted or unsubstituted. It is a 2-3 member heteroalkylene. In the embodiment, L3 is independently a substituted 2-3 member heteroalkylene. It is an alkylene. In the embodiment, L3 is independently an unsubstituted 2-3 member heteroalkylene. Yes. In the embodiment, L3 is independently a substituted or unsubstituted 4-5 member heteroalkylene. In the embodiment, L3 is independently a substituted 4- to 5-membered heteroalkylene. L3 is independently an unsubstituted 4-5 member heteroalkylene.

[0301] In this embodiment, L4 is bonded to -N(R23)-, -O-, -S-, -C(O)-, - N(R23)C(O)-, -C(O)N(R24)-, -N(R23)C(O)N(R2 4)-, -C(O)O-, -OC(O)-, -N(R23)C(O)O-, -OC(O) N(R24)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25)-O-, -OP(S)(R25)-O-, -OP(O)(NR23R24)- N-, -OP(S)(NR23R24)-N-, -OP(O)(NR23R24)- O-, -OP(S)(NR23R24)-O-, -P(O)(NR23R24)-N- , -P(S)(NR23R24)-N-, -P(O)(NR23R24)-O-, -P( S)(NR23R24)-O-, -SS-, substituted or unsubstituted alkylene, substituted or unsubstituted alkylene k is an unsubstituted heteroalkylene, a substituted or unsubstituted cycloalkylene, or a substituted or unsubstituted cycloalkylene. Substituting heterocycloalkyls, substituted or unsubstituted arylenes, or substituted or unsubstituted he It is terrorarylene.

[0302] In the embodiment, L4 is a bond. In the embodiment, L4 is -N(R23)-. In the embodiment, L4 is -O- or -S-. In the embodiment, L4 is -C(O )-. In the embodiment, L4 is -N(R23)C(O)- or -C(O)N(R 24)-. In this embodiment, L4 is -N(R23)C(O)N(R24)-. In the embodiment, L4 is -C(O)O- or -OC(O)-. L4 is -N(R23)C(O)O- or -OC(O)N(R24)-. (Implementation form) In this state, L4 is -OPO2-O-, -OP(O)(S)-O-, -OP(O)(R 25)-O-, -OP(O)(NR23R24)-N-, or OP(O)(NR2 It is 3R24)-O-. In the embodiment, L4 is -P(O)(NR23R24)-N- -P(S)(NR23R24)-N-, -P(O)(NR23R24)-O-, or It is -P(S)(NR23R24)-O-. In the embodiment, L4 is -SS-. .

[0303] In the embodiment, L4 is independently a substituted or unsubstituted alkylene (e.g., C1-C23) These are C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the application form, L4 independently substitutes alkylenes (e.g., C1-C23, C1-C12, These are C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L4 These are independently unsubstituted alkylenes (e.g., C1-C23, C1-C12, C1-C8, C 1-C6, C1-C4, or C1-C2). In this embodiment, L4 is independently placed It is a substituted or unsubstituted C1-C23 alkylene. In the embodiment, L4 is independently a substituted C It is a 1-C23 alkylene. In the embodiment, L4 is independently an unsubstituted C1-C23 alkylene. It is a chylene. In the embodiment, L4 is independently a substituted or unsubstituted C1-C12 alkylene. In this embodiment, L4 is independently a substituted C1-C12 alkylene. In this embodiment, L4 is independently an unsubstituted C1-C12 alkylene. In this embodiment, L4 is Independently, they are substituted or unsubstituted C1-C8 alkylenes. In the embodiment, L4 is independently And it is a substituted C1-C8 alkylene. In the embodiment, L4 is independently an unsubstituted C1-C 8. Alkylene. In the embodiment, L4 is independently substituted or unsubstituted C1-C6 alkylene. It is a chylene. In the embodiment, L4 is independently a substituted C1-C6 alkylene. In its morphology, L4 is independently an unsubstituted C1-C6 alkylene. In its embodiment, L4 is Independently, they are substituted or unsubstituted C1-C4 alkylenes. In the embodiment, L4 is independently And it is a substituted C1-C4 alkylene. In the embodiment, L4 is independently an unsubstituted C1-C 4 is alkylene. In the embodiment, L4 is independently substituted or unsubstituted ethylene. In the embodiment, L4 is independently substituted ethylene. In the embodiment, L4 is independently , unsubstituted ethylene. In the embodiment, L4 is independently substituted or unsubstituted methylene. Yes. In the embodiment, L4 is independently a substituted methylene group. In the embodiment, L4 is independently And it is an unsubstituted methylene group.

[0304] In the embodiment, L4 is independently a substituted or unsubstituted heteroalkylene (e.g., 2-2 (3 members, 2-12 members, 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members) In the embodiment, L4 is independently a substituted heteroalkylene (e.g., 2-23 member, 2-1 The number of members is 2, 2-8, 2-6, 4-6, 2-3, or 4-5. L4 is independently an unsubstituted heteroalkylene (e.g., 2-23 member, 2-12 member, 2- The members are 8, 2-6, 4-6, 2-3, or 4-5. In this embodiment, L4 is They are independently substituted or unsubstituted 2- to 23-membered heteroalkylenes. In the embodiment, L4 is Independently, it is a substituted 2- to 23-membered heteroalkylene. In the embodiment, L4 is independently non It is a substituted 2- to 23-membered heteroalkylene. In the embodiment, L4 is independently substituted or non-substituted. It is a substituted 2- to 8-membered heteroalkylene. In the embodiment, L4 is independently a substituted 2- to 8-membered heteroalkylene. It is a teloalkylene. In the embodiment, L4 is independently an unsubstituted 2-8 member heteroalkylene. In this embodiment, L4 is independently a substituted or unsubstituted 2-6 member heteroalkylene. In this embodiment, L4 is independently a substituted 2- to 6-membered heteroalkylene. In this embodiment, L4 is independently an unsubstituted 2- to 6-membered heteroalkylene. These are independently substituted or unsubstituted 4-6 member heteroalkylenes. In the embodiment, L4 is Independently, it is a substituted 4-6 member heteroalkylene. In the embodiment, L4 is independently non-substituted. It is a 4-6 member heteroalkylene. In the embodiment, L4 is independently substituted or unsubstituted. It is a 2-3 member heteroalkylene. In the embodiment, L4 is independently a substituted 2-3 member heteroalkylene. It is an alkylene. In the embodiment, L4 is independently an unsubstituted 2-3 member heteroalkylene. Yes. In the embodiment, L4 is independently a substituted or unsubstituted 4-5 member heteroalkylene. In the embodiment, L4 is independently a substituted 4- to 5-membered heteroalkylene. L4 is independently an unsubstituted 4-5 member heteroalkylene.

[0305] R23 is independently either hydrogen or an unsubstituted alkyl (e.g., C1-C23, C1-C12) , C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, R 23 is independently hydrogen. In the embodiment, R23 is independently unsubstituted C1-C23 In this embodiment, R23 is independently hydrogen or an unsubstituted C1-C12 alkyl group. In this embodiment, R23 is independently hydrogen or an unsubstituted C1-C10 alkyl group. Yes. In the embodiment, R23 is independently hydrogen or an unsubstituted C1-C8 alkyl group. In the embodiment, R23 is independently hydrogen or an unsubstituted C1-C6 alkyl group. In this embodiment, R23 is independently hydrogen or an unsubstituted C1-C4 alkyl group. R23 is independently either hydrogen or an unsubstituted C1-C2 alkyl group.

[0306] R24 is independently either hydrogen or an unsubstituted alkyl (e.g., C1-C24, C1-C12) , C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, R 24 is independently hydrogen. In the embodiment, R24 is independently unsubstituted C1-C24 In this embodiment, R24 is independently hydrogen or an unsubstituted C1-C12 alkyl group. In this embodiment, R24 is independently hydrogen or an unsubstituted C1-C10 alkyl group. Yes. In the embodiment, R24 is independently hydrogen or an unsubstituted C1-C8 alkyl group. In the embodiment, R24 is independently hydrogen or an unsubstituted C1-C6 alkyl group. In this embodiment, R24 is independently hydrogen or an unsubstituted C1-C4 alkyl group. R24 is independently either hydrogen or an unsubstituted C1-C2 alkyl group.

[0307] R25 is independently hydrogen or an unsubstituted alkyl (e.g., C1-C25, C1-C12) , C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, R 25 is independently hydrogen. In the embodiment, R25 is independently unsubstituted C1-C25 In this embodiment, R25 is independently hydrogen or an unsubstituted C1-C12 alkyl group. In this embodiment, R25 is independently hydrogen or an unsubstituted C1-C10 alkyl. Yes. In the embodiment, R25 is independently hydrogen or an unsubstituted C1-C8 alkyl group. In the embodiment, R25 is independently hydrogen or an unsubstituted C1-C6 alkyl group. In this embodiment, R25 is independently hydrogen or an unsubstituted C1-C4 alkyl group. R25 is independently either hydrogen or an unsubstituted C1-C2 alkyl group.

[0308] In this embodiment, L3 and L4 independently 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(C H3)2)-N-, -P(O)(N(CH3)2)-O-, -P(S)(N(CH3)2 )-N-, -P(S)(N(CH3)2)-O-, substituted or unsubstituted alkylenes, is a substituted or unsubstituted heteroalkylene. In the embodiment, L3 is independently bound, -NH-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OPO2-O- , -OP(O)(S)-O-, -OP(O)(CH3)-O-, -OP(S)(C H3)-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-, It is a substituted or unsubstituted alkylene, or a substituted or unsubstituted heteroalkylene. Morphologically, L4 is independent and bonded, -NH-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O)(C H3)-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 alkylene It is a substituted heteroalkylene.

[0309] In this embodiment, L3 is independent, [ka] In this embodiment, L3 is independently -OPO2-O-. In this embodiment, L3 Independently, -OP(O)(S)-O-. In the embodiment, L3 independently is -O -. In this embodiment, L3 is independently -S-.

[0310] In the embodiment, L3 binds to the 3' nitrogen of the morpholino moiety. Independently, is -C(O)-. In the embodiment, L3 is the 6' carbon of the morpholino moiety. It combines with -OP(O)(N(CH3)2)-N- In this embodiment, L3 is independently -OP(O)(N(CH3)2)-O- In this embodiment, L3 is independently -P(O)(N(CH3)2)-N-. Morphologically, L3 is independently -P(O)(N(CH3)2)-O-.

[0311] In this embodiment, L4 is independently a substituted or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene. In the embodiment, L4 is independently -L7-NH-C(O )- or -L7-C(O)-NH-. In the embodiment, L7 is independently substituted or These are unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L7 is independently a substituted alkylate. (For example, C1-C20, C1-C12, C1-C8, C1-C6, C1-C4, and (is C1-C2). In the embodiment, L7 is independently an unsubstituted alkylene (e.g., C 1-C20, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2) That is the case.

[0312] In the embodiment, L4 is independently a substituted or unsubstituted heteroalkylene (e.g., 2-2 (0-membered ring, 2-12 membered ring, 2-10 membered ring, 2-8 membered ring, 2-6 membered ring, or 2-4 membered ring) Yes. In the embodiment, L4 is independently a substituted heteroalkylene (e.g., a 2-20 membered ring). These are rings with 2 to 12 members, 2 to 10 members, 2 to 8 members, 2 to 6 members, or 2 to 4 members. In the application morphology, L4 independently comprises an oxo-substituted heteroalkylene (e.g., a 2-20 membered ring). These are rings with 2 to 12 members, 2 to 10 members, 2 to 8 members, 2 to 6 members, or 2 to 4 members. In the application morphology, L4 independently forms unsubstituted heteroalkylenes (e.g., 2-20 membered rings, 2-1 These are 2-membered rings, 2-10 membered rings, 2-8 membered rings, 2-6 membered rings, or 2-4 membered rings.

[0313] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted alkylene (e.g., C1-C20, These are C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). Morphologically, L4 is independently -L7-NH-C(O)-, and L7 is independently substituted. or unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C8, C1-C6) , C1-C4, or C1-C2). In this embodiment, L4 is independently -L7-C (O)-NH-, and L7 is independently a substituted or unsubstituted alkylene (e.g., C1- (C20, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2) ru.

[0314] In the embodiment, L7 is independently a substituted or unsubstituted alkylene (e.g., C1-C20 These are C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). In the application form, L7 independently substitutes alkylenes (e.g., C1-C20, C1-C12, These are C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, L7 These are independently unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C8, C 1-C6, C1-C4, or C1-C2). In this embodiment, L7 is independently placed It is a substituted or unsubstituted C1-C20 alkylene. In the embodiment, L7 is independently a substituted C It is a 1-C20 alkylene. In the embodiment, L7 is independently hydroxy(OH) substituted. It is a C1-C20 alkylene. In the embodiment, L7 is independently hydroxymethyl substituted. It is a C1-C20 alkylene. In the embodiment, L7 is independently an unsubstituted C1-C20 alkylene. It is lukilen. In the embodiment, L7 is independently a substituted or unsubstituted C1-C12 alkyl It is a len. In the embodiment, L7 is independently a substituted C1-C12 alkylene. Morphologically, L7 is independently a hydroxy(OH)-substituted C1-C12 alkylene. In the application, L7 is independently a hydroxymethyl-substituted C1-C12 alkylene. In the embodiment, L7 is independently an unsubstituted C1-C12 alkylene. In the embodiment, L 7 is independently a substituted or unsubstituted C1-C8 alkylene. In the embodiment, L7 is independently In this embodiment, L7 is independently a substituted C1-C8 alkylene. It is an (OH)-substituted C1-C8 alkylene. In the embodiment, L7 is independently a hydroxyl group. It is a methyl-substituted C1-C8 alkylene. In the embodiment, L7 is independently an unsubstituted C1- It is a C8 alkylene. In the embodiment, L7 is independently a substituted or unsubstituted C1-C6 It is a lukilen. In the embodiment, L7 is independently a substituted C1-C6 alkylene. In the application, L7 is independently a hydroxy(OH)-substituted C1-C6 alkylene. In the application form, L7 is independently a hydroxymethyl-substituted C1-C6 alkylene. In its morphology, L7 is independently an unsubstituted C1-C6 alkylene. In its embodiment, L7 is Independently, they are substituted or unsubstituted C1-C4 alkylenes. In the embodiment, L7 is independently The substituted C1-C4 alkylene is. In the embodiment, L7 is independently hydroxy(O H) Substituted C1-C4 alkylene. In the embodiment, L7 is independently hydroxymethyl L7 is a substituted C1-C4 alkylene. In this embodiment, L7 is independently an unsubstituted C1-C4 alkylene. It is an alkylene. In the embodiment, L7 is independently a substituted or unsubstituted C1-C2 alkylene. It is a len. In the embodiment, L7 is independently a substituted C1-C2 alkylene. Implementation In this state, L7 is independently a hydroxy(OH)-substituted C1-C2 alkylene. In this embodiment, L7 is independently a hydroxymethyl-substituted C1-C2 alkylene. Therefore, L7 is independently an unsubstituted C1-C2 alkylene.

[0315] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted alkylene (e.g., C1-C20, These are C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2). Morphologically, L4 is independently -L7-NH-C(O)- or -L7-C(O)-NH- In this embodiment, L7 is independently a substituted or unsubstituted C1-C8 alkylene. L4 is independently -L7-NH-C(O)- or -L7-C(O)-NH-, L7 is independently a substituted C1-C8 alkylene. In the embodiment, L4 is independently - It is L7-NH-C(O)- or -L7-C(O)-NH-, where L7 is independently hydroxyl It is a roxy(OH)-substituted C1-C8 alkylene. In the embodiment, L4 is independently -L It is 7-NH-C(O)- or -L7-C(O)-NH-, where L7 is independently Hydro It is a xymethyl-substituted C1-C8 alkylene. In the embodiment, L4 is independently -L7- It is NH-C(O)- or -L7-C(O)-NH-, where L7 is independently unsubstituted C1 -C8 alkylene.

[0316] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted C3-C8 alkylene. (Implementation) In this state, L4 is independently -L7-NH-C(O)- or -L7-C(O)-NH- In this embodiment, L7 is independently a substituted C3-C8 alkylene. Therefore, it is -L7-NH-C(O)- or -L7-C(O)-NH-, and L7 is independently , a hydroxy(OH) substituted C3-C8 alkylene. In the embodiment, L4 is independently , -L7-NH-C(O)- or -L7-C(O)-NH-, where L7 is independently It is a hydroxymethyl-substituted C3-C8 alkylene. In the embodiment, L4 is independently - It is L7-NH-C(O)- or -L7-C(O)-NH-, where L7 is independent and non-positional. This is a C3-C8 alkylene.

[0317] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted C5-C8 alkylene. (Implementation) In this state, L4 is independently -L7-NH-C(O)- or -L7-C(O)-NH- Yes, L7 is independently a substituted C5-C8 alkylene. In the embodiment, L4 is independently Therefore, it is -L7-NH-C(O)- or -L7-C(O)-NH-, and L7 is independently , a hydroxy(OH) substituted C5-C8 alkylene. In the embodiment, L4 is independently , -L7-NH-C(O)- or -L7-C(O)-NH-, where L7 is independently It is a hydroxymethyl-substituted C5-C8 alkylene. In the embodiment, L4 is independently - It is L7-NH-C(O)- or -L7-C(O)-NH-, where L7 is independent and non-positional. It is a C5-C8 alkylene.

[0318] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted octylene. In the embodiment, L 4 is independently -L7-NH-C(O)- or -L7-C(O)-NH-, and L7 L4 is independently a substituted octylene. In the embodiment, L4 is independently -L7-NH-C It is (O)- or -L7-C(O)-NH-, where L7 is independently hydroxy(OH) It is a substituted octylene. In the embodiment, L4 is independently -L7-NH-C(O)- and It is -L7-C(O)-NH-, and L7 is independently an unsubstituted octylene. (Implementation form) In this state, L4 is independently -L7-NH-C(O)-, and L7 is independently hydroxyl It is a cy(OH)-substituted octylene. In the embodiment, L4 is independently -L7-NH-C( The molecule is O)-, and L7 is independently a hydroxymethyl-substituted octylene. In the embodiment, L4 is independently -L7-NH-C(O)-, and L7 is independently unsubstituted octyle It is.

[0319] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted heptylene. In the embodiment, L 4 is independently -L7-NH-C(O)- or -L7-C(O)-NH-, and L7 L4 is independently a substituted heptylene. In the embodiment, L4 is independently -L7-NH-C It is (O)- or -L7-C(O)-NH-, where L7 is independently hydroxy(OH) It is a substituted heptylene. In the embodiment, L4 is independently -L7-NH-C(O)- and It is -L7-C(O)-NH-, and L7 is independently an unsubstituted heptylene. (Implementation form) In this state, L4 is independently -L7-NH-C(O)-, and L7 is independently hydroxyl It is a cy(OH)-substituted heptylene. In the embodiment, L4 is independently -L7-NH-C( The molecule is O)-, and L7 is independently a hydroxymethyl-substituted heptylene. In the embodiment, L4 is independently -L7-NH-C(O)-, and L7 is independently unsubstituted heptylene It is.

[0320] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted hexylene. In the embodiment, L 4 is independently -L7-NH-C(O)- or -L7-C(O)-NH-, and L7 L4 is independently a substituted hexylene. In the embodiment, L4 is independently -L7-NH-C It is (O)- or -L7-C(O)-NH-, where L7 is independently hydroxy(OH) It is a substituted hexylene. In the embodiment, L4 is independently -L7-NH-C(O)- and The compound is -L7-C(O)-NH-, where L7 is independently unsubstituted hexylene. (Implementation form) In this state, L4 is independently -L7-NH-C(O)-, and L7 is independently hydroxyl It is a cy(OH)-substituted hexylene. In the embodiment, L4 is independently -L7-NH-C( The molecule is O)-, and L7 is independently a hydroxymethyl-substituted hexylene. In the embodiment, L4 is independently -L7-NH-C(O)-, and L7 is independently unsubstituted hexyl It is.

[0321] In this embodiment, L4 is independently -L7-NH-C(O)- or -L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted pentylene. In the embodiment, L 4 is independently -L7-NH-C(O)- or -L7-C(O)-NH-, and L7 L4 is independently a substituted pentylene. In the embodiment, L4 is independently -L7-NH-C It is (O)- or -L7-C(O)-NH-, where L7 is independently hydroxy(OH) It is a substituted pentylene. In the embodiment, L4 is independently -L7-NH-C(O)- and It is -L7-C(O)-NH-, and L7 is independently an unsubstituted pentylene. (Implementation form) In this state, L4 is independently -L7-NH-C(O)-, and L7 is independently hydroxyl It is a cy(OH)-substituted pentylene. In the embodiment, L4 is independently -L7-NH-C( The molecule is O)-, and L7 is independently a hydroxymethyl-substituted pentylene. In the embodiment, L4 is independently -L7-NH-C(O)-, and L7 is independently unsubstituted pentylene It is.

[0322] In this embodiment, L4 is independently, [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] That is the case.

[0323] In this embodiment, L4 is independently, [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] In this embodiment, L4 is independently [ka] That is the case.

[0324] In this embodiment, -L3-L4- is independently -L7-NH-C(O)- or -L7- It is C(O)-NH-. In the embodiment, L7 is independently substituted or unsubstituted heteroal Chilen (for example, 2-20 member rings, 2-12 member rings, 2-10 member rings, 2-8 member rings, 2-6 member rings) , or a 2-4 membered ring). In the embodiment, L7 is independently a substituted heteroalkylene ( For example, 2-20 membered rings, 2-12 membered rings, 2-10 membered rings, 2-8 membered rings, 2-6 membered rings, or It is a 2-4 membered ring. In the embodiment, L7 is independently an oxo-substituted heteroalkylene ( For example, 2-20 membered rings, 2-12 membered rings, 2-10 membered rings, 2-8 membered rings, 2-6 membered rings, or It is a 2-4 membered ring. In the embodiment, L7 is independently an unsubstituted heteroalkylene (e.g., , 2-20 membered ring, 2-12 membered ring, 2-10 membered ring, 2-8 membered ring, 2-6 membered ring, or 2-4 (membered ring). In the embodiment, L7 is independently a substituted or unsubstituted heteroalkenylene ( For example, 2-20 membered rings, 2-12 membered rings, 2-10 membered rings, 2-8 membered rings, 2-6 membered rings, or It is a 2-4 membered ring. In the embodiment, L7 is independently a substituted heteroalkenylene (e.g. , 2-20 membered ring, 2-12 membered ring, 2-10 membered ring, 2-8 membered ring, 2-6 membered ring, or 2-4 (membered ring). In the embodiment, L7 is independently an oxo-substituted heteroalkenylene (for example) For example, a 2-20 member ring, a 2-12 member ring, a 2-10 member ring, a 2-8 member ring, a 2-6 member ring, or 2- It is a 4-membered ring. In the embodiment, L7 is independently a substituted heteroalkenylene (e.g., 2 ~20-membered rings, 2-12-membered rings, 2-10-membered rings, 2-8-membered rings, 2-6-membered rings, or 2-4-membered rings )

[0325] In the embodiment, L7 is independently a substituted or unsubstituted 2- to 20-membered heteroalkylene. In the embodiment, L7 is independently a substituted 2- to 20-membered heteroalkylene. In this embodiment, L7 is independently an oxo-substituted 2- to 20-membered heteroalkylene. L7 is independently an unsubstituted 2- to 20-membered heteroalkylene. In the embodiment, L7 is independently The resulting 2- to 12-membered heteroalkylene is either substituted or unsubstituted. In the embodiment, L7 is independently The substituted 2- to 12-membered heteroalkylenes. In the embodiment, L7 is independently oxo - Substituted 2- to 12-membered heteroalkylene. In the embodiment, L7 is independently an unsubstituted 2- It is a 12-membered heteroalkylene. In the embodiment, L7 is independently substituted or unsubstituted 2~ It is a 10-membered heteroalkylene. In the embodiment, L7 is independently a substituted 2- to 10-membered heteroalkylene. It is an alkylene. In the embodiment, L7 is independently an oxo-substituted 2- to 10-membered heteroal It is a kylene. In the embodiment, L7 is independently an unsubstituted 2- to 10-membered heteroalkylene. In the embodiment, L7 is independently a substituted or unsubstituted 2- to 8-membered heteroalkylene. In the embodiment, L7 is independently a substituted 2- to 8-membered heteroalkylene. L7 is independently an oxo-substituted 2- to 8-membered heteroalkylene. In the embodiment, L7 These are independently unsubstituted 2-8 member heteroalkylenes. In the embodiment, L7 is independently It is a substituted or unsubstituted 2-6 member heteroalkylene. In the embodiment, L7 is independently placed It is a 2-6 member heteroalkylene. In the embodiment, L7 is independently an oxo-substituted 2- It is a 6-membered heteroalkylene. In the embodiment, L7 is independently an unsubstituted 2-6 membered heteroalkylene. It is lucilene. In the embodiment, L7 is independently a substituted or unsubstituted 2-4 member heteroal. It is a kylene. In the embodiment, L7 is independently a substituted 2- to 4-membered heteroalkylene. In the embodiment, L7 is independently an oxo-substituted 2- to 4-membered heteroalkylene. In this state, L7 is independently an unsubstituted 2-4 member heteroalkylene.

[0326] In the embodiment, L7 is independently a substituted or unsubstituted 2-20 member heteroalkenylene. In the embodiment, L7 is independently a substituted 2- to 20-membered heteroalkenylene. In this embodiment, L7 is independently an oxo-substituted 2- to 20-membered heteroalkenylene. In this embodiment, L7 is independently an unsubstituted 2- to 20-membered heteroalkenylene. 7 is independently a substituted or unsubstituted 2- to 12-membered heteroalkenylene. In embodiments, L7 is independently a substituted 2- to 12-membered heteroalkenylene. In the embodiment, L7 is independently The resulting oxo-substituted 2-12 member heteroalkenylene is an oxo-substituted heteroalkenylene. In the embodiment, L7 is independently The unsubstituted 2- to 12-membered heteroalkenylenes. In the embodiment, L7 is independently substituted Or an unsubstituted 2- to 10-membered heteroalkenylene. In the embodiment, L7 is independently placed It is a 2- to 10-membered heteroalkenylene. In the embodiment, L7 is independently oxo-substituted. It is a 2- to 10-membered heteroalkenylene. In the embodiment, L7 is independently an unsubstituted 2- to 10 It is a heteroalkenylene. In the embodiment, L7 is independently substituted or unsubstituted 2-8 It is a 2-8 member heteroalkenylene. In the embodiment, L7 is independently a substituted 2-8 member heteroalkenylene. It is kenylene. In the embodiment, L7 is independently an oxo-substituted 2-8 member heteroalkene. It is a len. In the embodiment, L7 is independently an unsubstituted 2- to 8-membered heteroalkenylene. In the embodiment, L7 is independently a substituted or unsubstituted 2- to 6-membered heteroalkenylene. In the embodiment, L7 is independently a substituted 2- to 6-membered heteroalkenylene. In this embodiment, L7 is independently an oxo-substituted 2- to 6-membered heteroalkenylene. L7 is independently an unsubstituted 2- to 6-membered heteroalkenylene. In the embodiment, L7 is independently The resulting 2-4 member heteroalkenylene is either substituted or unsubstituted. In the embodiment, L7 is independently The substituted 2-4 member heteroalkenylene is used. In the embodiment, L7 is independently oxo - Substituted 2- to 4-membered heteroalkenylene. In the embodiment, L7 is independently an unsubstituted 2- It is a four-membered heteroalkenylene.

[0327] In this embodiment, -L3-L4- is independently -O-L7-NH-C(O)- or -O -L7-C(O)-NH-. In the embodiment, L7 is independently substituted or unsubstituted. Lukilen (for example, C1-C20, C1-C12, C1-C8, C1-C6, C1-C4) , or C1-C2). In this embodiment, -L3-L4- is independently, -O-L7- It is NH-C(O)- or -O-L7-C(O)-NH-, where L7 is independently substituted. or unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C8, C1-C6) , C1-C4 or C1-C2). In this embodiment, -L3-L4- are independently -O-L7-NH-C(O)-, where L7 is independently a substituted or unsubstituted alkylene ( For example, C1-C20, C1-C12, C1-C8, C1-C6, C1-C4, or C 1-C2) is. In this embodiment, -L3-L4- is independently -O-L7-C(O)- It is NH-, and L7 is independently a substituted or unsubstituted alkylene (e.g., C1-C20, These are C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2.

[0328] In this embodiment, -L3-L4- is independently -O-L7-C(O)-NH-, and L 7 is independently a substituted or unsubstituted C1-C8 alkylene. In the embodiment, -L3- L4- is independently -O-L7-C(O)-NH-, and L7 is independently substituted C1- It is a C8 alkylene. In the embodiment, -L3-L4- is independently -O-L7-C(O )-NH-, and L7 is independently a hydroxy(OH)-substituted C1-C8 alkylene. In this embodiment, -L3-L4- is independently -O-L7-C(O)-NH-, L7 is independently a hydroxymethyl-substituted C1-C8 alkylene. In embodiments, - L3-L4- is independently -O-L7-C(O)-NH-, and L7 is independently non-positional. This is a C1-C8 alkylene.

[0329] In this embodiment, -L3-L4- is independently -O-L7-C(O)-NH-, and L 7 is independently a substituted or unsubstituted C3-C8 alkylene. In the embodiment, -L3- L4- is independently -O-L7-C(O)-NH-, and L7 is independently substituted C3- It is a C8 alkylene. In the embodiment, -L3-L4- is independently -O-L7-C(O )-NH-, and L7 is independently a hydroxy(OH)-substituted C3-C8 alkylene. In this embodiment, -L3-L4- is independently -O-L7-C(O)-NH-, L7 is independently a hydroxymethyl-substituted C3-C8 alkylene. In embodiments, - L3-L4- is independently -O-L7-C(O)-NH-, and L7 is independently non-positional. This is a C3-C8 alkylene.

[0330] In this embodiment, -L3-L4- is independently -O-L7-C(O)-NH-, and L 7 is independently a substituted or unsubstituted C5-C8 alkylene. In the embodiment, -L3- L4- is independently -O-L7-C(O)-NH-, and L7 is independently substituted C5- It is a C8 alkylene. In the embodiment, -L3-L4- is independently -O-L7-C(O )-NH-, and L7 is independently a hydroxy(OH)-substituted C5-C8 alkylene. In this embodiment, -L3-L4- is independently -O-L7-C(O)-NH-, L7 is independently a hydroxymethyl-substituted C5-C8 alkylene. In embodiments, - L3-L4- is independently -O-L7-C(O)-NH-, and L7 is independently non-positional. It is a C5-C8 alkylene.

[0331] In this embodiment, -L3-L4- is independently -O-L7-NH-C(O)-, and L 7 is independently a substituted or unsubstituted C1-C8 alkylene. In the embodiment, -L3- L4- is independently -O-L7-NH-C(O)-, and L7 is independently substituted C1- It is a C8 alkylene. In the embodiment, -L3-L4- is independently -O-L7-NH- It is C(O)-, and L7 is independently a hydroxy(OH)-substituted C1-C8 alkylene. In this embodiment, -L3-L4- is independently -O-L7-NH-C(O)-, L7 is independently a hydroxymethyl-substituted C1-C8 alkylene. In embodiments, - L3-L4- is independently -O-L7-NH-C(O)-, and L7 is independently non-positional. This is a C1-C8 alkylene.

[0332] In this embodiment, -L3-L4- is independently -O-L7-NH-C(O)-, and L 7 is independently a substituted or unsubstituted C3-C8 alkylene. In the embodiment, -L3- L4- is independently -O-L7-NH-C(O)-, and L7 is independently substituted C3- It is a C8 alkylene. In the embodiment, -L3-L4- is independently -O-L7-NH- It is C(O)-, and L7 is independently a hydroxy(OH)-substituted C3-C8 alkylene. In this embodiment, -L3-L4- is independently -O-L7-NH-C(O)-, L7 is independently a hydroxymethyl-substituted C3-C8 alkylene. In embodiments, - L3-L4- is independently -O-L7-NH-C(O)-, and L7 is independently non-positional. This is a C3-C8 alkylene.

[0333] In this embodiment, -L3-L4- is independently -O-L7-NH-C(O)-, and L 7 is independently a substituted or unsubstituted C5-C8 alkylene. In the embodiment, -L3- L4- is independently -O-L7-NH-C(O)-, and L7 is independently substituted C5- It is a C8 alkylene. In the embodiment, -L3-L4- is independently -O-L7-NH- It is C(O)-, and L7 is independently a hydroxy(OH)-substituted C5-C8 alkylene. In this embodiment, -L3-L4- is independently -O-L7-NH-C(O)-, L7 is independently a hydroxymethyl-substituted C5-C8 alkylene. In embodiments, - L3-L4- is independently -O-L7-NH-C(O)-, and L7 is independently non-positional. It is a C5-C8 alkylene.

[0334] In this embodiment, -L3-L4- are independent of each other. [ka] In this embodiment, -L3-L4- are independent of each other. [ka] In this embodiment, -L3-L4- are independent of each other. [ka] In this embodiment, -L3-L4- are independent of each other. [ka] That is the case.

[0335] In this embodiment, -L3-L4- is independently -OPO2-O-L7-NH-C(O)- , -OP(O)(S)-O-L7-NH-C(O)-, -OPO2-O-L7-C(O) It is -NH- or -OP(O)(S)-O-L7-C(O)-NH- in the embodiment. L7 is independently of substituted or unsubstituted alkylenes (e.g., C1-C20, C1-C1 2, C1-C8, C1-C6, C1-C4, or C1-C2). In the embodiment, -L3-L4- are independent of -OPO2-O-L7-NH-C(O)- or -OP(O )(S)-O-L7-NH-C(O)-, where L7 is independently substituted or unsubstituted. It is chelene. In the embodiment, -L3-L4- is independently -OPO2-O-L7-NH It is -C(O)-, and L7 is independently a substituted or unsubstituted alkylene. In the embodiment, -L3-L4- is independent of -OP(O)(S)-O-L7-NH-C(O)- L7 is independently a substituted or unsubstituted alkylene. In the embodiment, -L3-L4 - is independent of -OPO2-O-L7-C(O)-NH- or -OP(O)(S)-O The structure is -L7-C(O)-NH-, where L7 is independently a substituted or unsubstituted alkylene. In this embodiment, -L3-L4- is independently -OPO2-O-L7-C(O)-NH- And L7 is independently a substituted or unsubstituted alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independently They are either substituted or unsubstituted alkylenes.

[0336] In this embodiment, -L3-L4- is independently -OPO2-O-L7-NH-C(O)- Alternatively, it is -OPO2-O-L7-C(O)-NH-, where L7 is independently substituted or non Substitutive alkylenes (e.g., C1-C20, C1-C12, C1-C8, C1-C6, C1 -C4, or C1-C2). In the embodiment, -L3-L4- are independently -OP The structure is O2-O-L7-NH-C(O)-, where L7 is independently a substituted or unsubstituted alkylate. (For example, C1-C20, C1-C12, C1-C8, C1-C6, C1-C4, and (C1-C2). In this embodiment, -L3-L4- are independently -OPO2-OL It is 7-C(O)-NH-, and L7 is independently a substituted or unsubstituted alkylene (e.g., C1-C20, C1-C12, C1-C8, C1-C6, C1-C4, or C1-C2 )

[0337] In this embodiment, -L3-L4- is independently -OP(O)(S)-O-L7-NH-C (O)- or -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independent. And, substituted or unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C8, These are C1-C6, C1-C4, or C1-C2). In this embodiment, -L3-L4- is Independently, -OP(O)(S)-O-L7-NH-C(O)-, and L7 independently, Substituted or unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C8, C1 -C6, C1-C4, or C1-C2). In the embodiment, -L3-L4- are independent. Thus, -OP(O)(S)-O-L7-C(O)-NH-, where L7 is independently substituted. or unsubstituted alkylenes (e.g., C1-C20, C1-C12, C1-C8, C1-C 6. C1-C4, or C1-C2).

[0338] In this embodiment, -L3-L4- is independently -OPO2-O-L7-C(O)-NH- In this embodiment, L7 is independently a substituted or unsubstituted C1-C8 alkylene. -L3-L4- is independently -OPO2-O-L7-C(O)-NH-, and L7 is Independently, it is a substituted C1-C8 alkylene. In the embodiment, -L3-L4- is independently , -OPO2-O-L7-C(O)-NH-, where L7 is independently hydroxy(OH ) Substituted C1-C8 alkylene. In the embodiment, -L3-L4- is independently -OP The structure is O2-O-L7-C(O)-NH-, where L7 is independently a hydroxymethyl-substituted C1 -C8 alkylene. In the embodiment, -L3-L4- is independently -OPO2-O- The structure is L7-C(O)-NH-, where L7 is independently an unsubstituted C1-C8 alkylene.

[0339] In this embodiment, -L3-L4- are independently -OP(O)(S)-O-L7-C(O) It is -NH-, and L7 is independently a substituted or unsubstituted C1-C8 alkylene. Morphologically, -L3-L4- is independent of -OP(O)(S)-O-L7-C(O)-NH -L7 is independently a substituted C1-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independently In other words, it is a hydroxy(OH)-substituted C1-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independently In this embodiment, it is a hydroxymethyl-substituted C1-C8 alkylene. 4- is independent, -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independent Therefore, it is an unsubstituted C1-C8 alkylene.

[0340] In this embodiment, -L3-L4- is independently -OPO2-O-L7-C(O)-NH- L7 is independently a substituted or unsubstituted C3-C8 alkylene. In the embodiment, -L3-L4- is independently -OPO2-O-L7-C(O)-NH-, and L7 is Independently, it is a substituted C3-C8 alkylene. In the embodiment, -L3-L4- is independently , -OPO2-O-L7-C(O)-NH-, where L7 is independently hydroxy(OH ) Substituted C3-C8 alkylene. In the embodiment, -L3-L4- is independently -OP The structure is O2-O-L7-C(O)-NH-, where L7 is independently a hydroxymethyl-substituted C3. -C8 alkylene. In the embodiment, -L3-L4- is independently -OPO2-O- The structure is L7-C(O)-NH-, where L7 is independently an unsubstituted C3-C8 alkylene.

[0341] In this embodiment, -L3-L4- are independently -OP(O)(S)-O-L7-C(O) It is -NH-, and L7 is independently a substituted or unsubstituted C3-C8 alkylene. Morphologically, -L3-L4- is independent of -OP(O)(S)-O-L7-C(O)-NH -L7 is independently a substituted C3-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independently In other words, it is a hydroxy(OH)-substituted C3-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independently In this embodiment, it is a hydroxymethyl-substituted C3-C8 alkylene. 4- is independent, -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independent Therefore, it is an unsubstituted C3-C8 alkylene.

[0342] In this embodiment, -L3-L4- is independently -OPO2-O-L7-C(O)-NH- In this embodiment, L7 is independently a substituted or unsubstituted C5-C8 alkylene. -L3-L4- is independently -OPO2-O-L7-C(O)-NH-, and L7 is Independently, it is a substituted C5-C8 alkylene. In the embodiment, -L3-L4- is independently , -OPO2-O-L7-C(O)-NH-, where L7 is independently hydroxy(OH ) Substituted C5-C8 alkylene. In the embodiment, -L3-L4- is independently -OP The structure is O2-O-L7-C(O)-NH-, where L7 is independently a hydroxymethyl-substituted C5. -C8 alkylene. In the embodiment, -L3-L4- is independently -OPO2-O- It is L7-C(O)-NH-, and L7 is independently an unsubstituted C5-C8 alkylene.

[0343] In this embodiment, -L3-L4- are independently -OP(O)(S)-O-L7-C(O) It is -NH-, and L7 is independently a substituted or unsubstituted C5-C8 alkylene. Morphologically, -L3-L4- is independent of -OP(O)(S)-O-L7-C(O)-NH -L7 is independently a substituted C5-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independently In other words, it is a hydroxy(OH)-substituted C5-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independently In this embodiment, it is a hydroxymethyl-substituted C5-C8 alkylene. 4- is independent, -OP(O)(S)-O-L7-C(O)-NH-, and L7 is independent Therefore, it is an unsubstituted C5-C8 alkylene.

[0344] In this embodiment, -L3-L4- is independently -OPO2-O-L7-NH-C(O)- In this embodiment, L7 is independently a substituted or unsubstituted C1-C8 alkylene. -L3-L4- are independently -OPO2-O-L7-NH-C(O)-, and L7 is Independently, it is a substituted C1-C8 alkylene. In the embodiment, -L3-L4- is independently , -OPO2-O-L7-NH-C(O)-, where L7 is independently hydroxy(OH) ) Substituted C1-C8 alkylene. In the embodiment, -L3-L4- is independently -OP The structure is O2-O-L7-NH-C(O)-, where L7 is independently a hydroxymethyl-substituted C1 -C8 alkylene. In the embodiment, -L3-L4- is independently -OPO2-O- It is L7-NH-C(O)-, and L7 is independently an unsubstituted C1-C8 alkylene.

[0345] In this embodiment, -L3-L4- is independently -OP(O)(S)-O-L7-NH-C (O)-, and L7 is independently a substituted or unsubstituted C1-C8 alkylene. Morphologically, -L3-L4- are independent of -OP(O)(S)-O-L7-NH-C(O) -L7 is independently a substituted C1-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)2-O-L7-NH-C(O)-, and L7 is Independently, these are hydroxy(OH)-substituted C1-C8 alkylenes. In the embodiment, -L3 -L4- is independently -OP(O)(S)-O-L7-NH-C(O)-, and L7 is Independently, these are hydroxymethyl-substituted C1-C8 alkylenes. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-NH-C(O)-, and L7 is independently In other words, it is an unsubstituted C1-C8 alkylene.

[0346] In this embodiment, -L3-L4- is independently -OPO2-O-L7-NH-C(O)- L7 is independently a substituted or unsubstituted C3-C8 alkylene. In the embodiment, -L3-L4- are independently -OPO2-O-L7-NH-C(O)-, and L7 is Independently, it is a substituted C3-C8 alkylene. In the embodiment, -L3-L4- is independently , -OPO2-O-L7-NH-C(O)-, where L7 is independently hydroxy(OH) ) Substituted C3-C8 alkylene. In the embodiment, -L3-L4- is independently -OP The structure is O2-O-L7-NH-C(O)-, where L7 is independently a hydroxymethyl-substituted C3. -C8 alkylene. In the embodiment, -L3-L4- is independently -OPO2-O- It is L7-NH-C(O)-, and L7 is independently an unsubstituted C3-C8 alkylene.

[0347] In this embodiment, -L3-L4- is independently -OP(O)(S)-O-L7-NH-C (O)-, and L7 is independently a substituted or unsubstituted C3-C8 alkylene. Morphologically, -L3-L4- are independent of -OP(O)(S)-O-L7-NH-C(O) -L7 is independently a substituted C3-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-NH-C(O)-, and L7 is independently In other words, it is a hydroxy(OH)-substituted C3-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-NH-C(O)-, and L7 is independently In this embodiment, it is a hydroxymethyl-substituted C3-C8 alkylene. 4- is independent, -OP(O)(S)-O-L7-NH-C(O)-, and L7 is independent Therefore, it is an unsubstituted C3-C8 alkylene.

[0348] In this embodiment, -L3-L4- is independently -OPO2-O-L7-NH-C(O)- In this embodiment, L7 is independently a substituted or unsubstituted C5-C8 alkylene. -L3-L4- are independently -OPO2-O-L7-NH-C(O)-, and L7 is Independently, it is a substituted C5-C8 alkylene. In the embodiment, -L3-L4- is independently , -OPO2-O-L7-NH-C(O)-, where L7 is independently hydroxy(OH) ) Substituted C5-C8 alkylene. In the embodiment, -L3-L4- is independently -OP The structure is O2-O-L7-NH-C(O)-, where L7 is independently a hydroxymethyl-substituted C5. -C8 alkylene. In the embodiment, -L3-L4- is independently -OPO2-O- It is L7-NH-C(O)-, and L7 is independently an unsubstituted C5-C8 alkylene.

[0349] In this embodiment, -L3-L4- is independently -OP(O)(S)-O-L7-NH-C (O)-, and L7 is independently a substituted or unsubstituted C5-C8 alkylene. Morphologically, -L3-L4- are independent of -OP(O)(S)-O-L7-NH-C(O) -L7 is independently a substituted C5-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-NH-C(O)-, and L7 is independently In other words, it is a hydroxy(OH)-substituted C5-C8 alkylene. In the embodiment, -L3- L4- is independently -OP(O)(S)-O-L7-NH-C(O)-, and L7 is independently In this embodiment, it is a hydroxymethyl-substituted C5-C8 alkylene. 4- is independent, -OP(O)(S)-O-L7-NH-C(O)-, and L7 is independent Therefore, it is an unsubstituted C5-C8 alkylene.

[0350] In this embodiment, -L3-L4- is bonded to the 3' carbon of the oligonucleotide. In this state, -L3-L4- is the 3' nitrogen of the oligonucleotide (for example, the morpholino portion). It binds to the 3' nitrogen of the oligonucleotide. In this embodiment, -L3-L4- is the 5' nitrogen of the oligonucleotide. It bonds with carbon. In the embodiment, -L3-L4- is the 6' carbon of the oligonucleotide (e.g. For example, it bonds with the 6' carbon of the morpholino moiety. In this embodiment, -L3-L4- is It binds to the 2' carbon of the oligonucleotide. In this embodiment, -L3-L4- is oligonucleotide It binds to the nucleic acid base of rheotide.

[0351] In the embodiment, at least -L3-L4- are the 3' carbon of the oligonucleotide at the 3' end. It binds to an element. In the embodiment, at least -L3-L4- is an oligonucleotide at the 3' end. It binds to the 3' nitrogen of the cydide (for example, the 3' nitrogen of the morpholino moiety). In the embodiment, At the very least, -L3-L4- will bond to the 5' carbon of the oligonucleotide at its 5' end. Morphologically, at least -L3-L4- is the 6' carbon of the oligonucleotide at the 5' end (e.g.) For example, it bonds to the 6' carbon of the morpholino portion.

[0352] In this embodiment, -L3-L4- are independent of each other. [ka] That is the case.

[0353] In this embodiment, -L3-L4- are independent of each other. [ka] In this embodiment, -L3-L4- are independent of each other. [ka] In this embodiment, -L3-L4- are independent of each other. [ka] In this embodiment, -L3-L4- are independent of each other. [ka] In this embodiment, -L3-L4- are independent of each other. [ka] That is the case.

[0354] In this embodiment, -L3-L4- are independent of each other. [ka] It then bonds to the 3' carbon of the oligonucleotide. In this embodiment, -L3-L4- independently bond to the 3' carbon of the oligonucleotide. [ka] In this embodiment, -L3-L4- is independently bonded to the 3' carbon of the oligonucleotide. to combine, [ka] That is the case.

[0355] In this embodiment, -L3-L4- are independent of each other. [ka] It binds to the 3' nitrogen of the oligonucleotide (for example, the 3' nitrogen of the morpholino portion). do. In the embodiment, -L3-L4- is independently the 3' nitrogen of the oligonucleotide (e.g., mo It binds to the 3' nitrogen of the refolino portion. [ka] In the embodiment, -L3-L4- is independently the 3' nitrogen of the oligonucleotide (e.g. For example, it binds to the 3' nitrogen of the morpholino portion. [ka] That is the case.

[0356] In this embodiment, -L3-L4- are independent of each other. [ka] It is bonded to the 5' carbon of the oligonucleotide. In the embodiment, -L3-L4- is German Standing upright, it bonds to the 5' carbon of the oligonucleotide. [ka] In this embodiment, -L3-L4- is independently bonded to the 5' carbon of the oligonucleotide. to combine, [ka] That is the case.

[0357] In embodiments in which the oligonucleotide includes a morpholino moiety, L3 is independently -P( It is either O)(N(CH3)2)-N- or -P(O)(N(CH3)2)-O-. In its morphology, L4 is a substituted or unsubstituted heterocycloalkyl. In this embodiment, L4 is a substituted heterocycloalkyl. In this embodiment, L4 is an unsubstituted heterocycloalkyl This is a kill. In the embodiment, L4 is a substituted or unsubstituted piperidinylene. Embodiment In this embodiment, L4 is a substituted piperidine. In the embodiment, L4 is a substituted or unsubstituted piperazinerene. In this embodiment, L4 is a substituted piperazinerene. In this embodiment, -L3-L4- is independently the 6' carbon of the oligonucleotide (e.g. For example, it bonds to the 6' carbon of the morpholino portion. [ka] In this embodiment, -L3-L4- is independently the 6' carbon of the oligonucleotide (e.g. For example, it bonds to the 6' carbon of the morpholino portion. [ka] In this embodiment, -L3-L4- is independently the 6' carbon of the oligonucleotide (e.g. For example, it bonds to the 6' carbon of the morpholino portion. [ka] That is the case.

[0358] In the embodiment, -L3-L4- independently bind to the nucleic acid base of the oligonucleotide. In this embodiment, -L3-L4- are independent of each other. [ka] It binds to the nucleic acid base of an oligonucleotide.

[0359] In this embodiment, -L3-L4- is a double-stranded oligonucleotide at either of its 3' ends. It bonds to the 3' carbon of the do. In the embodiment, -L3-L4- is the 3' of its antisense chain. It binds to the 3' carbon of the double-stranded oligonucleotide at the terminal. In this embodiment, -L3-L4- Its sense strand binds to the 3' carbon of the double-stranded oligonucleotide at its 3' end.

[0360] In this embodiment, -L3-L4- is a double-stranded oligonucleotide at either of its 3' ends. It binds to the 3' nitrogen of the do (for example, the 3' nitrogen of the morpholino moiety). In the embodimen...

Claims

1. A compound containing nucleic acid (A) covalently bonded to a half-life extension motif (HLEM).

2. The aforementioned compound has formula (I), (HLEM)z-A (I), The compound according to claim 1, wherein z is an integer from 1 to 5.

3. The compound according to claim 1, wherein the nucleic acid is covalently bonded to an incorporation motif (UM).

4. The aforementioned compound has formula (II), (HLEM)z-A-(UM)t (II), The compound according to claim 3, wherein t is an integer from 1 to 5 in the formula.

5. The aforementioned half-life extension motif has the following structure: 【Chemistry 1】 During the ceremony, L1 is an independent covalent linker, L2 is independently an unsubstituted alkylene. The compound according to claim 1, wherein k is an integer from 1 to 5.

6. L1 is L1A-L1B-L1C-L1D-L1E, L2 is an unsubstituted C2-C22 alkylene. L1A, L1B, L1C, L1D, and L1E are independently coupled, -N(R20)- , -O-, -S-, -C(O)-, -N(R20)C(O)-, -C(O)N(R21) -, -N(R20)C(O)N(R21)-, -C(O)O-, -OC(O)-, -N( R20)C(O)O-, -OC(O)N(R21)-, -OPO2-O-, -OP(O )(S)-O-, -O-P(O)(R22)-O-, -O-P(S)(R22)-O-, -OP(O)(NR20R21)-N-, -OP(S)(NR20R21)-N-, -OP(O)(NR20R21)-O-, -OP(S)(NR20R21)-O-, -P(O)(NR20R21)-N-, -P(S)(NR20R21)-N-, -P(O )(NR20R21)-O-, -P(S)(NR20R21)-O-, -S-S-, substitution Alternatively, unsubstituted alkylenes, substituted or unsubstituted heteroalkylenes, substituted or unsubstituted. Cycloalkylenes, substituted or unsubstituted heterocycloalkylenes, substituted or unsubstituted a reylene, or substituted or unsubstituted heteroarylene, Each of R20, R21, and R22 independently contains hydrogen or an unsubstituted C1-C10 alkyl group. The compound according to claim 5, which is a compound.

7. The compound according to claim 5, wherein the maximum dimension of L1 is less than 200 angstroms.

8. The compound according to claim 5, wherein the longest linear atomic path L1 has a length of 1 to 60 atoms.

9. The maximum dimensions of each of L1A, L1B, L1C, L1D, and L1E are independent of each other, The compound according to claim 6, wherein the angstrom is less than 0 angstroms.

10. Each of L1A, L1B, L1C, L1D, and L1E independently has a length of 1 to 20 atoms. The compound according to claim 6.

11. Each of R20, R21, and R22 is independently hydrogen or unsubstituted C1-C3 aluminum The compound according to claim 1, which is a kill compound.

12. The compound according to claim 1, wherein the nucleic acid is an oligonucleotide.

13. The present invention according to claim 12, wherein one L1A is bonded to the 3' carbon of the oligonucleotide. compound.

14. The present invention according to claim 12, wherein one L1A is bonded to the 3' nitrogen of the oligonucleotide. compound.

15. The present invention according to claim 12, wherein one L1A is bonded to the 5' carbon of the oligonucleotide. compound.

16. The present invention according to claim 12, wherein one L1A is bonded to the 6' carbon of the oligonucleotide. compound.

17. The present invention according to claim 12, wherein one L1A is bonded to the 2' carbon of the oligonucleotide. compound.

18. The present invention according to claim 12, wherein one L1A is bound to the nucleic acid base of the oligonucleotide. compound.

19. L1A independently produces -O-, -C(O)-, -C(O)O-, -OC(O)-, -OP O2-O-, -O-P(O)(S)-O-, -O-P(O)(CH3)-O-, -O-P (S)(CH3)-O-, -O-P(O)(N(CH3)2)-N-, -O-P(O)( N(CH3)2)-O-, -O-P(S)(N(CH3)2)-N-, -O-P(S)( N(CH3)2)-O-, -P(O)(N(CH3)2)-N-, -P(O)(N(CH 3) 2) -O-, -P(S) (N(CH3)2) -N-, -P(S) (N(CH3)2) -O-, substituted or unsubstituted alkylenes, or substituted or unsubstituted heteroalkylenes A compound according to claim 6.

20. L1A became independent, 【Chemistry 2】 The compound according to claim 6.

21. L1A is independently -OPO2-O- or -OP(O)(S)-O-, claim The compound described in item 6.

22. The compound according to claim 6, wherein L1A is independently -O-.

23. The compound according to claim 6, wherein L1A is independently -C(O)-.

24. According to claim 6, L1A is independently -O-P(O)(N(CH3)2)-N- A compound of [unclear].

25. L1B independently forms substituted or unsubstituted alkylenes, or substituted or unsubstituted heterozymes. The compound according to claim 6, which is alkylene.

26. L1B independently operates as -L10-NH-C(O)- or -L10-C(O)-NH-. The compound according to claim 6, wherein L10 is a substituted or unsubstituted alkylene.

27. L1B became independent, 【Transformation 3】 The compound according to claim 6.

28. L1B became independent, 【Chemistry 4】 The compound according to claim 6.

29. L1B became independent, 【Transformation 5】 And, w1 is an integer between 0 and 10. w2 is an integer between 0 and 5, w3 is an integer between 0 and 5. The compound according to claim 6, wherein w4 is an integer from 0 to 5.

30. L1B became independent, 【Chemistry 6-1】 【Chemistry 6-2】 And, w1 is an integer between 0 and 10. The compound according to claim 6, wherein w2 is an integer from 0 to 5.

31. L1B became independent, 【Transformation 7】 The compound according to claim 6.

32. L1B became independent, 【Transformation 8】 The compound according to claim 6.

33. -L1A-L1B- independently becomes -O-L10-NH-C(O)- or -O-L10 It is -C(O)-NH-, and L10 is independently a substituted or unsubstituted alkylene, and also substituted. Alternatively, it may be an unsubstituted heteroalkylene, or a substituted or unsubstituted heteroalkene. The compound according to claim 6.

34. -L1A-L1B- independently constitutes -O-L10-NH-C(O)-, and L10 independently The compound according to claim 6, wherein it is a substituted or unsubstituted C5-C8 alkylene.

35. -L1A-L1B- are independent, 【Chemistry 9】 The compound according to claim 6.

36. -L1A-L1B- independently becomes -OPO2-O-L10-NH-C(O)-, -OP (O)(S)-O-L10-NH-C(O)-, -OPO2-O-L10-C(O)-N H-, or -OP(O)(S)-O-L10-C(O)-NH-, where L10 is independent The compound according to claim 6, wherein it is a substituted or unsubstituted alkylene.

37. -L1A-L1B- independently becomes -OPO2-O-L10-NH-C(O)- or - OP(O)(S)-O-L10-NH-C(O)-, where L10 is independently substituted or The compound according to claim 6, wherein is an unsubstituted C5-C8 alkylene.

38. -L1A-L1B- are independent, 【Chemistry 10】 The compound according to claim 6.

39. -L1A-L1B- are independent, 【Chemistry 11】 The compound according to claim 12, wherein it is bonded to the 3' carbon of the oligonucleotide.

40. -L1A-L1B- are independent, 【Chemistry 12】 And, The compound according to claim 12, wherein it is bonded to the 3' nitrogen of the oligonucleotide.

41. -L1A-L1B- are independent, 【Chemistry 13】 The compound according to claim 12, wherein it is bonded to the 5' carbon of the oligonucleotide.

42. -L1A-L1B- are independent, 【Chemistry 14】 The compound according to claim 12, wherein it is bonded to the 6' carbon of the oligonucleotide.

43. -L1A-L1B- independently binds to the nucleic acid base of the alkyl group, claim The compound described in item 12.

44. L1C independently forms substituted or unsubstituted alkylenes, or substituted or unsubstituted heterozymes. It is alkylene, L1D independently binds, substitutes, or unsubstituted alkylenes, or substituted or unsubstituted heterozymes. Alkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene n and L1E independently binds, substitutes, or unsubstituted heteroalkylenes, or -NHC(O The compound according to claim 6, wherein the compound is as follows:

45. L1C independently consists of a substituted or unsubstituted C1-C10 alkylene, or a substituted or These are unsubstituted 2- to 10-membered heteroalkylenes. L1D can independently bond, substitute, or unsubstituted C1-C10 alkylenes, or substitutes. Alternatively, they are unsubstituted 2- to 10-membered heteroalkylenes. L1E independently binds, is substituted, or is unsubstituted in 2- to 10-membered heteroalkylenes, or - The compound according to claim 6, wherein it is NHC(O)-.

46. L1C independently forms a substituted or unsubstituted C1-C7 alkylene, or a substituted or unsubstituted C1-C7 alkylene. Substituting 5-8 member heteroalkylenes, L1D independently binds, is substituted or unsubstituted with C1-C7 alkylenes, or is substituted. k is an unsubstituted 5-8 member heteroalkylene, L1E can independently bind, substitute, or unsubstituted 5- to 8-membered heteroalkylenes, or -N The compound according to claim 6, wherein it is HC(O)-.

47. L1C independently forms R1C-substituted or unsubstituted C1-C7 alkylene, or R1C - Substituted or unsubstituted 5- to 8-membered heteroalkylenes, L1D independently binds, R1D-substituted or unsubstituted C1-C7 alkylenes, or R1D-substituted or unsubstituted 5- to 8-membered heteroalkylenes, L1E can independently bind, R1E-substituted or unsubstituted 5-8 member heteroalkylenes, It is -NHC(O)-, R1C is independently oxo, or -L8C-L2C-R8C, R1D is independently oxo, or -L8D-L2D-R8D, R1E is independently oxo, or -L8E-L2E-R8E, Each L8C, L8D, and L8E independently undergoes bonding, substitution, or non-substitution of C1-C6. Lukilen, or a substituted or unsubstituted 2-6 member heteroalkylene, Each L2C, L2D, and L2E is independently a bonded or unsubstituted alkylene. Each of R8C, R8D, and R8E independently consists of hydrogen, a substituted or unsubstituted alkyl group, and The compound according to claim 6, wherein it is a substituted or unsubstituted heteroalkyl group.

48. The aforementioned half-life extension motif has the following structure: 【Chemistry 15】 In the formula, L8A independently represents a bonded, substituted, or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene, The compound according to claim 47, wherein L2A is independently a bonded or unsubstituted alkylene. 。

49. The aforementioned half-life extension motif has the following structure: 【Chemistry 16】 In the formula, L8A independently represents a bonded, substituted, or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene, The compound according to claim 47, wherein L2A is independently a bonded or unsubstituted alkylene. 。

50. The aforementioned half-life extension motif has the following structure: 【Chemistry 17】 In the formula, L8A independently represents a bonded, substituted, or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene, The compound according to claim 47, wherein L2A is independently a bonded or unsubstituted alkylene. 。

51. The aforementioned half-life extension motif has the following structure: [Chemistry 18] In the formula, L8A independently represents a bonded, substituted, or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene, The compound according to claim 47, wherein L2A is independently a bonded or unsubstituted alkylene. 。

52. The aforementioned half-life extension motif has the following structure: 【Chemistry 19】 In the formula, L8A independently represents a bonded, substituted, or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene, The compound according to claim 47, wherein L2A is independently a bonded or unsubstituted alkylene. 。

53. The aforementioned half-life extension motif has the following structure: 【Chemistry 20】 In the formula, L8A independently represents a bonded, substituted, or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene, The compound according to claim 47, wherein L2A is independently a bonded or unsubstituted alkylene. 。

54. The aforementioned half-life extension motif has the following structure: 【Chemistry 21】 In the formula, L8A independently represents a bonded, substituted, or unsubstituted alkylene, or a substituted or It is an unsubstituted heteroalkylene, The compound according to claim 47, wherein L2A is independently a bonded or unsubstituted alkylene. 。

55. R1C is independent and is -NHC(O)-L2C-R8C, L2C is independently bonded or unsubstituted C2-C22 alkylene. R8C is independently hydrogen, an unsubstituted C1-C3 alkyl group, or a -COOH group, claim The compound described in item 47.

56. R1C is independent and is -NHC(O)-L2C-R8C, L2C is independent, and it is a coupling. The compound according to claim 47, wherein R8C is independently an unsubstituted C1-C3 alkyl group.

57. R1C is independent and is -NHC(O)-L2C-R8C, L2C is independently an unsubstituted C10-C22 alkylene. Claim 47, where R8C is independently an unsubstituted C1-C3 alkyl or -COOH. The compounds described above.

58. R1D is independent and is -NHC(O)-L2D-R8D, L2D is independently bonded or unsubstituted C2-C22 alkylene. R8D is independently hydrogen, an unsubstituted C1-C3 alkyl group, or a -COOH group, claim The compound described in item 47.

59. R1E is independent and is -NHC(O)-L2E-R8E, L2E is independently bonded or unsubstituted C2-C22 alkylene. R8E is independently hydrogen, an unsubstituted C1-C3 alkyl group, or a -COOH group, claim The compound described in item 47.

60. L1C is independently R1C-substituted or unsubstituted C3-C7 alkylene. L1D is independently bonded or unsubstituted arylene. L1E independently forms R1E-substituted or unsubstituted 5- to 8-membered heteroalkylenes, or - The compound according to claim 47, wherein it is NHC(O)-.

61. L1C is independently an R1C-substituted or unsubstituted 5- to 8-membered heteroalkylene. L1D can independently bind, or R1D-substituted or unsubstituted 5- to 8-membered heteroalkylates. n and L1E independently forms R1E-substituted or unsubstituted 5- to 8-membered heteroalkylenes, or - NHC(O)-, Each R1C, R1D, or R1E is independently oxo or -COOH, in the claim. The compound described in item 47.

62. L1C is independently an R1C-substituted C2-C5 alkyl group. L1D is independently an unsubstituted phenylene or an unsubstituted biphenylene. L1E independently forms R1E-substituted or unsubstituted 5- to 8-membered heteroalkylenes, or - NHC(O)-, R1C is independent and is -NHC(O)-L2C-R8C, L2C is independently bonded or unsubstituted C10-C22 alkylene. R8C is independently an unsubstituted C1-C3 alkyl group or a -COOH group. The compound according to claim 47, wherein R1E is an oxo.

63. L1C is independently R1C-substituted or unsubstituted ethylene, or n-pentylene. the law of nature, L1D is independent, and is a combination. L1E is independent and is -NHC(O)-, R1C is independent and is -NHC(O)-L2C-R8C, L2C is independently bonded or unsubstituted C10-C22 alkylene. Claim 47, where R8C is independently an unsubstituted C1-C3 alkyl or -COOH. The compounds described above.

64. L1C is independently R1C-substituted or unsubstituted n-pentylene, L1D is independently an oxo-substituted or unsubstituted 5- to 8-membered heteroalkylene. L1E is independent and is -NHC(O)-, R1C is independent and is -NHC(O)-L2C-R8C, L2C is independently bonded or unsubstituted C10-C22 alkylene. Claim 47, where R8C is independently an unsubstituted C1-C3 alkyl or -COOH. The compounds described above.

65. L1C is independently R1C-substituted methylene, L1D is independent, and is a combination. L1E is independent and is -NHC(O)-, R1C is independent, and is -L8C-L2C-R8C. L8C independently forms unsubstituted C1-C6 alkylenes or oxo-substituted 2- to 12-member heterozymes. It is alkylene, L2C is independent, and it is a coupling. R8C independently forms an unsubstituted C1-C6 alkyl or oxo-substituted 2-12 member heteroa The compound according to claim 47, which is lukil.

66. R8C independently comprises unsubstituted C1-C6 alkyl or oxo- and C1-C15 alkyl The compound according to claim 65, wherein it is a Kill-substituted 2- to 12-membered heteroalkyl group.

67. L1 is 【Chemistry 22-1】 【Chemistry 22-2】 【Chemistry 22-3】 【Chemistry 22-4】 The compound according to claim 5.

68. Each L2, L2A, L2C, L2D, or L2E independently forms a non-substituted C2-C22 aluminum alloy. A compound according to any one of claims 48 to 57, wherein the compound is a kylene.

69. Each L2, L2A, L2C, L2D, or L2E independently has a non-substituted C5-C22 aluminum alloy. The compound according to claim 68, which is a kylene.

70. Each L2, L2A, L2C, L2D, or L2E independently has a non-substituted C10-C22 The compound according to claim 68, which is ruquilen.

71. Each of L2, L2A, L2C, L2D, or L2E is an unsubstituted C12-C22 alkylene. The compound according to claim 68.

72. Each of L2, L2A, L2C, L2D, or L2E is an unsubstituted C12-C18 alkylene. The compound according to claim 68.

73. Each of L2, L2A, L2C, L2D, or L2E is an unsubstituted C12-C16 alkylene. The compound according to claim 68.

74. Each of L2, L2A, L2C, L2D, or L2E is an unsubstituted C14-C15 alkylene. The compound according to claim 68.

75. Each L2, L2A, L2C, L2D, or L2E is a non-substituting, non-branched C10-C22 The compound according to claim 68, which is a kylene.

76. Each L2, L2A, L2C, L2D, or L2E is a non-substituting, non-branched C12-C22 The compound according to claim 68, which is a kylene.

77. Each L2, L2A, L2C, L2D, or L2E is a non-substituting, non-branched C12-C18 aluminum alloy. The compound according to claim 68, which is a kylene.

78. Each L2, L2A, L2C, L2D, or L2E is a non-substituting, non-branched C12-C16 The compound according to claim 68, which is a kylene.

79. Each L2, L2A, L2C, L2D, or L2E is a non-substituting, non-branched C14-C15 The compound according to claim 68, which is a kylene.

80. Each L2, L2A, L2C, L2D, or L2E is an unsubstituted, unbranched saturated C10-C22 The compound according to claim 68, which is alkylene.

81. Each L2, L2A, L2C, L2D, or L2E is an unsubstituted, unbranched saturated C12-C22 The compound according to claim 68, which is alkylene.

82. Each L2, L2A, L2C, L2D, or L2E is an unsubstituted, unbranched saturated C12-C18 The compound according to claim 68, which is alkylene.

83. Each L2, L2A, L2C, L2D, or L2E is an unsubstituted, unbranched saturated C12-C16 The compound according to claim 68, which is alkylene.

84. Each L2, L2A, L2C, L2D, or L2E is an unsubstituted, unbranched saturated C14-C15 The compound according to claim 68, which is alkylene.

85. The compound according to claim 5, comprising one to five arbitrarily different half-life extension motifs.

86. The compound according to claim 5, comprising only one half-life extension motif.

87. The aforementioned incorporated motif independently has the following structure: 【Chemistry 23】 During the ceremony, L3 and L4 independently bond, -N(R23)-, -O-, -S-, -C(O)- , -N(R23)C(O)-, -C(O)N(R24)-, -N(R23)C(O)N( R24)-, -C(O)O-, -OC(O)-, -N(R23)C(O)O-, -OC( O)N(R24)-, -OPO2-O-, -OP(O)(S)-O-, -OP(O) (R25) -O-, -O-P(S) (R25) -O-, -O-P(O) (NR23R24 ) -N-, -O-P(S) (NR23R24) -N-, -O-P(O) (NR23R24 ) -O-, -O-P(S) (NR23R24) -O-, -P(O) (NR23R24)- N-, -P(S)(NR23R24)-N-, -P(O)(NR23R24)-O-, - P(S)(NR23R24)-O-,-S-S-, substituted or unsubstituted alkylene, substituted Or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or Unsubstituted heterocycloalkyl, substituted or unsubstituted arylene, or substituted or unsubstituted It is a heteroarylene, L5 is -L5A-L5B-L5C-L5D-L5E-, L6 is -L6A-L6B-L6C-L6D-L6E-, R1 and R2 are independently unsubstituted C1-C25 alkyl groups, and R1 and R2 At least one of them is an unsubstituted C9-C19 alkyl group, R3 is hydrogen, -NH2, -OH, -SH, -C(O)H, -C(O)NH2, -NH C(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 is an unsubstituted aryl, or a substituted or unsubstituted heteroaryl. L5A, L5B, L5C, L5D, L5E, L6A, L6B, L6C, L6D, and L6E independently forms bonds: -NH-, -O-, -S-, -C(O)-, -NHC(O)- , -NHC(O)NH-, -C(O)O-, -OC(O)-, -C(O)NH-, substitution also or unsubstituted alkylenes, substituted or unsubstituted heteroalkylenes, substituted or unsubstituted alkylenes Chloalkylenes, substituted or unsubstituted heterocycloalkylenes, substituted or unsubstituted ali -Lene, or substituted or unsubstituted heteroarylene, Each of R23, R24, and R25 independently contains hydrogen or unsubstituted C1-C10 alkyl The compound according to claim 3.

88. The compound according to claim 4, wherein t is 1.

89. The compound according to claim 4, wherein t is 2.

90. The compound according to claim 4, wherein t is 3.

91. Each of R23, R24, and R25 is independently hydrogen or unsubstituted C1-C3 aluminum The compound according to claim 4, which is a kill compound.

92. The chemical compound according to claim 87, wherein one L3 is bonded to the 3' carbon of the oligonucleotide. Compound.

93. The chemical compound according to claim 87, wherein one L3 is bonded to the 3' nitrogen of the oligonucleotide. Compound.

94. The chemical compound according to claim 87, wherein one L3 is bonded to the 5' carbon of the oligonucleotide. Compound.

95. The chemical compound according to claim 87, wherein one L3 is bonded to the 6' carbon of the oligonucleotide. Compound.

96. The chemical formula according to claim 87, wherein one L3 is bound to the nucleic acid base of the oligonucleotide. Compound.

97. L3 and L4 independently form bonds: -NH-, -O-, -C(O)-, -C(O)O- , -OC(O)-, -OPO2-O-, -OPO2-O-(S)-O-, -O-P(O)( CH3)-O-, -O-P(S)(CH3)-O-, -O-P(O)(N(CH3)2) -N-, -O-P(O) (N(CH3)2) -O-, -O-P(S) (N(CH3)2) -N-, -O-P(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 The compound according to claim 87, which is an unsubstituted heteroalkylene.

98. L3 became independent, 【Chemistry 24】 The compound according to claim 87.

99. Claim that L3 is independently -OPO2-O- or -OP(O)(S)-O- The compound described in 87.

100. The compound according to claim 87, wherein L3 is independently -O-.

101. The compound according to claim 87, wherein L3 is independently -C(O)-.

102. Claim 87 states that L3 is independently -O-P(O)(N(CH3)2)-N- A compound of [unclear].

103. L4 independently determines whether it is a substituted or unsubstituted alkylene, or a substituted or unsubstituted hetero The compound according to claim 87, which is ruquilen.

104. L4 is independently -L7-NH-C(O)- or -L7-C(O)-NH- The compound according to claim 87, wherein L7 is a substituted or unsubstituted alkylene.

105. L4 becomes independent, 【Chemistry 25】 The compound according to claim 87.

106. L4 becomes independent, 【Chemistry 26】 The compound according to claim 87.

107. -L3-L4- independently becomes -O-L7-NH-C(O)- or -O-L7-C( O)-NH-, and L7 independently consists of a substituted or unsubstituted alkylene, substituted or non Claim 8, which is a substituted heteroalkylene, or a substituted or unsubstituted heteroalkenylene. The compound described in 7.

108. -L3-L4- independently forms -O-L7-NH-C(O)-, and L7 independently forms The compound according to claim 107, which is a substituted or unsubstituted C5-C8 alkylene.

109. L3 and L4 operate independently. 【Chemistry 27】 The compound according to claim 108.

110. -L3-L4- independently becomes -OPO2-O-L7-NH-C(O)-, -OP(O) (S)-O-L7-NH-C(O)-, -OPO2-O-L7-C(O)-NH-, and is -OP(O)(S)-O-L7-C(O)-NH-, where L7 is independently substituted or The compound according to claim 87, wherein is an unsubstituted alkylene.

111. -L3-L4- independently becomes -OPO2-O-L7-NH-C(O)- or -OP (O)(S)-O-L7-NH-C(O)-, where L7 is independently substituted or unsubstituted. The compound according to claim 110, which is a C5-C8 alkylene.

112. L3 and L4 operate independently. 【Chemistry 28】 The compound according to claim 111.

113. L3 and L4 operate independently. 【Chemistry 29】 The compound according to claim 112, wherein it is bonded to the 3' carbon of an oligonucleotide.

114. L3 and L4 operate independently. 【Transformation 30】 And, The compound according to claim 112, which is bonded to the 3' nitrogen of the oligonucleotide.

115. L3 and L4 operate independently. 【Chemistry 31】 The compound according to claim 112, wherein it is bonded to the 5' carbon of the oligonucleotide.

116. L3 and L4 operate independently. 【Chemistry 32】 The compound according to claim 112, wherein it is bonded to the 6' carbon of the oligonucleotide.

117. L3 and L4 operate independently. 【Transformation 33】 The compound according to claim 112, wherein it binds to the nucleic acid base of the oligonucleotide.

118. The compound according to any one of claims 87 to 117, wherein R3 is independently hydrogen.

119. L6 independently produces -NHC(O)-, -C(O)NH-, substituted or unsubstituted alkylates. Any of claims 87 to 118, which is a heteroalkylene, or a substituted or unsubstituted heteroalkylene. The compound described in item 1.

120. The compound according to claim 119, wherein L6 is independently -NHC(O)-.

121. L6A is independently a bonded or unsubstituted alkylene. L6B is independently a bond, -NHC(O)-, or an unsubstituted arylene. L6C is independently a bond, an unsubstituted alkylene, or an unsubstituted arylene. L6D is independently a bonded or unsubstituted alkylene. The compound according to claim 119, wherein L6E is independently bonded or -NHC(O)- thing.

122. L6A is independently bonded or unsubstituted C1-C8 alkylene. L6B is independently a bond, -NHC(O)-, or unsubstituted phenylene. L6C can independently bond, unsubstituted C2-C8 alkynylene, or unsubstituted phenylene. can be, L6D is independently bonded or unsubstituted C1-C8 alkylene. The compound according to claim 119, wherein L6E is independently bonded or -NHC(O)- thing.

123. L6 operates independently, and then connects. 【Transformation 34】 The compound according to claim 87.

124. L5 independently produces -NHC(O)-, -C(O)NH-, substituted or unsubstituted alkylates. The compound according to claim 87, which is a heteroalkylene, or a substituted or unsubstituted heteroalkylene.

125. The compound according to claim 87, wherein L5 is independently -NHC(O)-.

126. L5A is independently a bonded or unsubstituted alkylene. L5B is independently a bond, -NHC(O)-, or an unsubstituted arylene. L5C is independently a bond, an unsubstituted alkylene, or an unsubstituted arylene. L5D is independently a bonded or unsubstituted alkylene. The compound according to claim 87, wherein L5E is independently a bond or -NHC(O)- 。

127. L5A is independently bonded or unsubstituted C1-C8 alkylene. L5B is independently a bond, -NHC(O)-, or unsubstituted phenylene. L5C can independently bond, unsubstituted C2-C8 alkynylene, or unsubstituted phenylene. can be, L5D is independently bonded or unsubstituted C1-C8 alkylene. The compound according to claim 87, wherein L5E is independently a bond or -NHC(O)- 。

128. L5 is independent and combined, 【Chemistry 35】 The compound according to claim 87.

129. The compound according to claim 87, wherein R1 is an unsubstituted C1-C17 alkyl group.

130. The compound according to claim 87, wherein R1 is an unsubstituted C11-C17 alkyl group.

131. The compound according to claim 87, wherein R1 is an unsubstituted C13-C17 alkyl group.

132. The compound according to claim 87, wherein R1 is an unsubstituted C14-C15 alkyl group.

133. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched C1-C17 alkyl group.

134. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched C11-C17 alkyl group.

135. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched C13-C17 alkyl group.

136. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched C14-C15 alkyl group.

137. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched saturated C1-C17 alkyl group.

138. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched, saturated C11-C17 alkyl group. 。

139. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched, saturated C13-C17 alkyl group. 。

140. The compound according to claim 87, wherein R1 is an unsubstituted, unbranched, saturated C14-C15 alkyl group. 。

141. The compound according to claim 87, wherein R2 is an unsubstituted C1-C17 alkyl group.

142. The compound according to claim 87, wherein R2 is an unsubstituted C11-C17 alkyl group.

143. The compound according to claim 87, wherein R2 is an unsubstituted C13-C17 alkyl group.

144. The compound according to claim 87, wherein R2 is an unsubstituted C14-C15 alkyl group.

145. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched C1-C17 alkyl group.

146. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched C11-C17 alkyl group.

147. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched C13-C17 alkyl group.

148. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched C14-C15 alkyl group.

149. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched, saturated C1-C17 alkyl group.

150. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched, saturated C11-C17 alkyl group. 。

151. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched, saturated C13-C17 alkyl group. 。

152. The compound according to claim 87, wherein R2 is an unsubstituted, unbranched, saturated C14-C15 alkyl group. 。

153. The oligonucleotide is a single-stranded oligonucleotide or a double-stranded oligonucleotide. The compound according to claim 12, which is D.

154. The aforementioned double-stranded oligonucleotide is a small interfering RNA, a short hairpin RNA, and The compound according to claim 153, wherein is a microRNA mimetic.

155. The aforementioned single-stranded oligonucleotide is a single-stranded small interfering RNA, RNaseH oligonucleotide Rheotide, anti-microRNA oligonucleotide, sterically barrierd oligonucleotide, exo These are skipped oligonucleotides, CRISPR guide RNAs, or aptamers. The compound according to claim 153.

156. The compound according to claim 1, wherein the nucleic acid comprises one or more modified nucleotides.

157. The compound according to claim 1, wherein the nucleic acid comprises one or more modified sugar moieties.

158. The modified sugar portion includes 2' modification or unlock sugar modification, according to claim 157. Compound.

159. The 2'-modifications include 2'-fluoromodification, 2'-O-methyl modification, and 2'-O-methoxy modification. The compound according to claim 158, selected from ethyl and bicyclic sugar modification.

160. The bicyclic sugar modification is a 4'-CH(CH3)-O-2' bond, a 4'-(CH2)2-O -2' bond, 4'-CH(CH2-OMe)-O-2' bond, 4'-CH2-N(CH3 A choice between a )-O-2' bond and a 4'-CH2-N(H)-O-2' bond. The compound described in item 159.

161. The compound according to claim 157, wherein the modified sugar portion is a morpholino portion.

162. The compound according to claim 1, wherein the nucleic acid comprises one or more modified nucleotide interbonds.

163. The modified nucleotide interbonds are phosphorothioate bonds and phosphorodiamidites A compound according to claim 162, selected from the combinations.

164. The nucleic acid is a small interfering RNA (siRNA) or a single-stranded small interfering RNA (ssR NA i) and the 5' carbon at the 5' end of the antisense chain is a hydroxyl group, a phosphate group The compound according to claim 156, or comprising a modified phosphate group.

165. The modified phosphate group is 5'-(E)-vinylphosphonate, as described in claim 164. nucleic acid compounds.

166. The aforementioned oligonucleotide comprises two strands, one containing a sense strand and the other containing an antisense strand hybridized with it. A chain oligonucleotide, wherein each of the antisense chain and the sense chain is independent of 1 The compound according to claim 154, having a length of 5 to 30 nucleotides.

167. Each of the antisense strand and sense strand is 17 to 25 nucleotides in length. The compound according to claim 166.

168. Each of the antisense strand and the sense strand has a length of 19 to 23 nucleotides. The compound according to claim 166.

169. The oligonucleotide is single-stranded, and the oligonucleotide has 8 to 30 nuclei The compound according to claim 154, wherein the length of the rheotide is the length of the compound.

170. The oligonucleotide is 12 to 25 nucleotides in length, as described in claim 169. The compound listed.

171. The oligonucleotide is 15 to 25 nucleotides in length, as described in claim 169. The compound listed.

172. The oligonucleotide is 17 to 23 nucleotides in length, as described in claim 169. The compound listed.

173. The compound according to claim 1, wherein the compound can bind to serum proteins.

174. The compound according to claim 1, wherein the compound can bind to serum albumin.

175. The compound is the same compound lacking one or more arbitrarily different half-life extension motifs. The compound according to claim 1, having increased serum albumin binding in comparison.

176. The compound is the same compound lacking one or more arbitrarily different half-life extension motifs. The compound according to claim 1, having a comparatively increased serum half-life.

177. The compound according to claim 1, wherein the compound further comprises a ligand.

178. Claim 177, wherein the ligand comprises a peptide, antibody, carbohydrate, or additional nucleic acid. The compounds described above.

179. The claim states that the incorporation motif includes a peptide, antibody, carbohydrate, or additional nucleic acid. The compounds described in item 3.

180. A method comprising contacting cells with the compound described in claim 1.

181. The method according to claim 180, wherein the contact occurs in vitro.

182. The method according to claim 180, wherein the contact occurs ex vivo.

183. The method according to claim 180, wherein the contact occurs in vivo.

184. A method comprising administering the compound described in claim 1 to a target.

185. The subject is a disease of the eye, liver, kidney, heart, adipose tissue, lung, muscle, or spleen or The method according to claim 184, which has a disability.

186. The compound according to claim 1 for use in treatment.

187. The compound according to claim 1, for use in the preparation of pharmaceuticals.

188. A method for introducing nucleic acids into cells within a target, wherein the compound described in claim 1 is introduced into the target. A method that includes giving in to something.

189. A cell comprising the compound described in claim 1.

190. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the compound described in claim 1.

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