Oligonucleotide delivery enhancers, pharmaceutical compositions and methods of using them

Abstract

The present invention provides a compound having a specific structure, which can substantially enhance the delivery efficiency of oligonucleotides to various subjects both in vitro and in vivo, thereby achieving improved regulation of target gene expression. Also disclosed are pharmaceutical compositions containing the compound and methods for regulating target gene expression using the same.

Description

Technical Field

[0001] The present disclosure relates to the technical field of gene regulation, and more particularly to unique compounds useful for enhancing the delivery efficiency of oligonucleotides both in vitro and in vivo.

Background Art

[0002] Oligonucleotide-based therapeutic agents are emerging technologies because their mechanism of action results in the regulation of expression in almost unlimited target genes. When an oligonucleotide is administered to a patient, an organ, a tissue, or one or more cells, it may cause or affect various biochemical reactions, and as a result, functions such as suppression, inhibition, activation, and regulation of gene expression are achieved. The opportunity to use oligonucleotide-based therapeutic agents is highly anticipated in terms of providing solutions to medical problems that could not be addressed by conventional pharmaceuticals. However, one of the main obstacles in the commercialization of oligonucleotide-based pharmaceuticals is the lack of an effective method for delivering them to appropriate organs, tissues, or cells. Oligonucleotide therapeutic agents typically have a molecular weight in the range of 7 kDa to 14 kDa and have a strong negative charge because their backbone contains phosphodiester or phosphorothioate. The relatively large molecular weight and high negative charge density prevent the transfer of oligonucleotides across cell membranes. Although many strategies have been developed to facilitate the transfer of oligonucleotides, the transfer efficiency remains a challenge.

Summary of the Invention

Problems to be Solved by the Invention

[0003] Therefore, there is still a long-standing need for the development of a unique technology that can deliver oligonucleotides with better efficiency to a wider range of organs, tissues, and cells, particularly those that were hardly reachable by conventional techniques.

[0004] As a result of intensive research, the company has developed a unique delivery enhancing compound that can achieve the above goals.

Means for Solving the Problems

[0005] The present disclosure provides an oligonucleotide delivery enhancing compound (DEC) comprising a nitrogen-containing 5-membered heterocyclic moiety. The DEC can be directly or indirectly linked to an oligonucleotide and can be used to enhance the delivery efficiency of the oligonucleotide to a subject both in vitro and in vivo. In certain embodiments, the DEC has a structure represented by Formula AI or Formula AII

[0006]

Chemical formula

[0007] In another specific embodiment, the oligonucleotide delivery enhancing compound comprises a moiety represented by Formula BI.

[0008]

Chemical formula

[0009] In another specific embodiment, the oligonucleotide delivery enhancing compound has a structure represented by Formula BII.

[0010]

Chemical formula

[0011] Also provided herein is an oligonucleotide delivery agent comprising a DEC moiety derived from the DEC of the present disclosure and at least one oligonucleotide, wherein the DEC moiety is directly or indirectly linked to the oligonucleotide via at least one linking moiety. The oligonucleotide can be an antisense oligonucleotide (ASO), antisense RNA, short interfering RNA (siRNA), microRNA (miRNA), small activating RNA (saRNA), double-stranded RNA (dsRNA), and small guide RNA (sgRNA).

[0012] Also provided is a pharmaceutical composition comprising the DEC of the present disclosure, which pharmaceutical composition may optionally contain additional ingredients such as pharmaceutically acceptable carriers, excipients, solvents, diluents, stabilizers, dispersants, buffers, solubilizers, preservatives, and combinations thereof.

[0013] Also provided herein is a method of regulating the expression of a target gene in a subject in vitro or in vivo, which method comprises administering the pharmaceutical composition of the present disclosure to the subject in the case of an in vivo assay or therapeutic treatment, and contacting the pharmaceutical composition with one or more cells in the case of an in vitro assay.

[0014] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory and are not restrictive of the invention, as claimed.

[0015] The features and advantages of the present invention can be better understood by reference to the following detailed description. In the following detailed description, exemplary embodiments utilizing the principles of the present invention are presented and described in conjunction with the accompanying drawings (Figure 1).

Brief Description of the Drawings

[0016]

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Mode for Carrying Out the Invention

[0017] The newly developed oligonucleotide delivery agent enables more efficient delivery of a desired amount or a higher level of oligonucleotides in the target tissue shown above, compared to the prior art oligonucleotide delivery technologies, and thus has the potential to improve biological activity and pharmacological properties (e.g., biodistribution, bioavailability, pharmacokinetics, activity, efficacy, etc.). In some embodiments, the improvement in biological activity properties may result in improved cell uptake, higher efficacy, and longer duration / half-life. In some embodiments, the improvement in pharmacological properties may also result in lower toxicity, lower dosage, less frequent administration, and less undesirable immune response. In some embodiments, the present oligonucleotide delivery agent includes a simpler synthesis process and has higher processability in manufacturing. In some embodiments, the present oligonucleotide delivery agent has the inherent pharmacological properties of free benzimidazole or benzimidazole derivatives that target proton pumps (reversible and irreversible proton pump inhibitors, as ppi), dopamine receptors (drd), angiotensin ii type 1 receptors (at1), histamine receptors (hrh), dual-specific mitogen-activated protein kinases (mek) and / or cyclin-dependent kinases (cdk), etc. In some embodiments, the present oligonucleotide delivery agent can potentially be used as a drug for peptic ulcer, hypertension, schizophrenia, parasitic infection, bacterial infection, viral infection, and cancer, etc., due to its inherent pharmacological properties.

[0018] In some embodiments, the novel developed oligonucleotide delivery agents disclosed herein can deliver and function an effective amount of oligonucleotides to target tissues or cells (e.g., central nervous system (e.g., brain and spinal cord), liver, lung, kidney, intestine, pancreas, gallbladder, heart, lymph node, spleen, stomach, bladder, muscle and bone). In some embodiments, the regulatory activity of the oligonucleotide delivery agent, e.g., the activity of upregulating or downregulating the expression of a target gene, can improve the expression of the target gene in cells as compared to the prior art in the art. Thus, based on the findings provided herein, those skilled in the art will, by using the oligonucleotide delivery agents described herein, as described above, promote the improved in vivo distribution of therapeutic oligonucleotides in various targets or cells for preventing, treating and / or delaying the onset of various diseases, disorders and / or conditions.

[0019] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Also, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference.

[0020] As disclosed herein, singular forms such as "a", "an", "the" include plural referents unless the context clearly dictates otherwise.

[0021] As disclosed in this disclosure, terms such as "about", "substantially", "approximately" are intended to have a broad meaning consistent with the ordinary usage by those of ordinary skill in the art relevant to the subject matter of this disclosure.

[0022] As disclosed in the present disclosure, "and / or" means "and, or alternatively". When a numerical range is indicated, the range includes the numerical values within the range (including the upper and lower limits) and sub-ranges within the range. For example, the range from 1 to 3 includes any of the numerical values 1, 2, 3, and the sub-ranges from 1 to 2 and from 2 to 3.

[0023] The terms "oligonucleotide", "polynucleotide", or "oligo" can be used interchangeably and refer to polymers of nucleotides, including single-stranded, double-stranded, or partially double-stranded DNA, RNA, or DNA / RNA hybrid single-stranded, double-stranded, or partially double-stranded nucleic acid molecules, oligonucleotide strands containing regularly and irregularly alternating deoxyribosyl and ribosyl moieties, and modifications for such oligonucleotides and natural or non-natural frameworks, but are not limited thereto. In one embodiment, the oligonucleotide can be selected from the group consisting of antisense oligonucleotides (ASOs), antisense RNAs, short interfering RNAs (siRNAs), microRNAs (miRNAs), small activating RNAs (saRNAs), dsRNAs, and small guide RNAs (sgRNAs).

[0024] As used herein, the terms "oligonucleotide strand", "strand", and "oligonucleotide sequence" can be used interchangeably and are, for example, less than 45, less than 40, less than 35, such as 2 - 50 bases, 5 - 45 bases, 10 - 40 bases, 15 - 35 bases, 20 - 30 bases (including nucleotides of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)). In some non-limiting examples, the length of the strand can be any length from 5 to 50 nucleotides, 10 to 40 nucleotides, 15 to 35 nucleotides, 18 to 30 nucleotides, or 20 to 25 nucleotides.

[0025] As used herein, the term "target gene" can refer to a nucleic acid sequence that occurs naturally in an organism, a foreign gene, a viral or bacterial sequence, a chromosomal or episomal gene, and / or one or more cells and / or chromatin that are transiently or stably transfected or integrated. The target gene can be a gene encoding a protein or a non-protein-coding gene such as a microRNA gene and a long non-coding RNA gene.

[0026] In embodiments of the present application, one target gene is SOD1. By definition, a "target sequence" refers to a sequence fragment to which the sense or antisense oligonucleotide of an siRNA or saRNA is homologous or complementary. For example, in certain embodiments, an SOD1 siRNA is homologous or complementary to a target selection sequence within a human SOD1 transcript.

[0027] As used herein, the term "guide strand" or "G strand" refers to the strand in a small RNA duplex that assembles with an Argonaute (AGO) protein. The other strand that is partially or fully complementary to the guide strand is called the "passenger strand" or "P strand". Without being limited to a particular theory, the strand having a sequence complementary to the target sequence is the antisense strand and, if appropriately designed, is preferentially selected as the guide strand. In this case, the passenger strand is the sense strand. However, a strand cannot be said to be a guide strand until its 5' end is captured within the MID domain of AGO2. Thus, the sense strand can be selected as the guide strand, resulting in an antisense passenger strand.

[0028] As used herein, the term "LNA" refers to a locked nucleic acid in which the 2'-oxygen atom and the 4'-carbon atom are linked by an extra bridge. As used herein, the term "BNA" refers to a 2'-O and 4'-aminoethylene bridged nucleic acid that may include a 5- or 6-membered bridged structure having an N-O bond. As used herein, the term "PNA" refers to a nucleic acid mimic having a pseudopeptide backbone consisting of N-(2-aminoethyl)glycine units having nucleobases linked to the glycine nitrogen via a carbonylmethylene linker.

[0029] As used herein, the term "antisense oligonucleotide" or "ASO" refers to a single-stranded oligonucleotide having, or comprising, or consisting of a base sequence that enables it to hybridize to a target molecule such as an oligonucleotide or other nucleic acid, modified nucleic acid, nucleic acid analog, etc., and can hybridize to a target molecule such as another nucleic acid, modified nucleic acid, nucleic acid analog, etc. by base pairing such as Watson-Crick type base pairs or non-Watson-Crick type base pairs. In some embodiments, the antisense oligonucleotide is completely or nearly completely complementary to the target molecule. In some embodiments, any type of oligonucleotide described herein or known in the art can be used as an antisense oligonucleotide. In various embodiments, the antisense oligonucleotide can perform or be involved in any of a variety of biological functions, including RNA interference, RNase H-mediated cleavage, exon skipping, prevention of exon skipping, enhancement or inhibition of factors that mediate binding to another nucleic acid (e.g., proteins, RNA, protein-RNA complexes, or other molecules), or other biological functions performed by the antisense oligonucleotide.

[0030] As used herein, the terms "short interfering RNA", "siRNA", and "inhibitory RNA (iRNA)" can be used interchangeably and refer to ribonucleic acid molecules that can down-regulate, knockdown, or silence target gene expression. They may be double-stranded nucleic acid molecules. siRNA mainly binds to target mRNA in the cytoplasm and reduces post-transcriptional gene expression via the RNA interference (RNAi) mechanism. siRNA mainly binds to target mRNA in the cytoplasm and down-regulates gene expression post-transcriptionally via the RNA interference (RNAi) mechanism. siRNA may be designed to target the mRNA sequence of a gene, for example, to silence its expression via the RNAi mechanism such as SOD1 in order to maximize the therapeutic effect in ALS patients. This modification does not cause loss of cell activity, but rather results in increased stability and increased cell activity. Examples of chemical modifications include phosphorothioate groups, 2'-deoxynucleotides, 2'-OCH3-containing ribonucleotides, 2'-F-ribonucleotides, 2'-methoxyethyl ribonucleotides, and combinations thereof. siRNAs can have various lengths (e.g., 10-200 bps) and structures (e.g., hairpin type, single-stranded / double-stranded / partially double-stranded, bulge, nick / gap, mismatch) and are processed intracellularly to provide active gene silencing. Double-stranded siRNAs may have the same number of nucleotides on each strand (blunt ends) or may have asymmetric ends (overhangs). For example, 1-2 nucleotide overhangs can be present on the sense strand and / or the antisense strand and can be present on the 5'- and / or 3'-ends of a given strand. The length of the siRNA molecule is typically about 10 to about 60, about 10 to about 50, about 15 to about 30, about 17 to about 29, about 18 to about 28, about 19 to about 27, about 20 to about 26, about 21 to about 25, and about 22 to about 24 base pairs, and is typically about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 23, about 25, about 30, about 40, or about 50 base pairs. Further, the terms "short interfering RNA", "RNA silencing", and "siRNA" include nucleic acids other than ribonucleotides, including but not limited to modified nucleotides or analogs.

[0031] As used herein, the terms "small activating RNA", "saRNA", and "small activating ribonucleic acid" can be used interchangeably and refer to ribonucleic acid molecules that can up-regulate the expression of a target gene. It can be a double-stranded nucleic acid molecule consisting of a first nucleic acid strand containing a ribonucleotide sequence having sequence homology with a non-coding nucleic acid sequence (such as a promoter or enhancer) of the target gene, and a second nucleic acid strand containing a nucleotide sequence complementary to the first nucleic acid strand. SaRNA can also be composed of synthetic or vector-expressed single-stranded RNA molecules that are prone to form hairpin structures by two complementary regions within the molecule. The first region contains a ribonucleotide sequence having sequence homology with the target sequence of the promoter of the gene, and the ribonucleotide sequence contained in the second region is complementary to the first region. The length of the double-stranded region of the saRNA molecule is typically about 10 to about 60, about 10 to about 50, about 10 to about 40, about 12 to about 30, about 14 to about 28, about 16 to about 26, about 18 to about 24, about 20 to about 22 base pairs, and is typically about 10, about 13, about 15, about 17, about 18, about 19, about 20, about 21, about 22, about 25, about 30, about 40, about 50, or about 60 base pairs. Further, the terms "small activating RNA", "saRNA", and "small activating ribonucleic acid" include nucleic acids other than ribonucleotides, including but not limited to modified nucleotides or analogs.

[0032] As used herein, the terms "O", "ODV", and "oligonucleotide delivery vehicle" are used synonymously and refer to oligonucleotide molecules containing double-stranded or duplex RNA (e.g., siRNA or saRNA), and auxiliary oligonucleotides (ACOs) covalently bound to the double-stranded RNA via a linker.

[0033] As used herein, the terms "delivery enhancing compound" and "DEC" are used interchangeably and refer to the compounds of the present disclosure.

[0034] As used herein, the terms "DEC-linked oligonucleotide" and "DCO" are used interchangeably and refer to a combination in which at least one moiety derived from DEC is attached to at least one oligonucleotide, for example by a covalent bond. Further, a DCO may include at least one target site that aids the oligonucleotide in binding to, accumulating in, or accessing a target cell or target site.

[0035] As used herein, the terms "administer", "parenteral administration", "administered" and "parenterally administered" have the meaning understood in the art to refer to normal enteral administration, topical administration, particularly injection administration, and include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intraarticular, subcutaneous, intradermal, intraperitoneal, intratracheal, epidural, intracardiac, intrapleural, intrathoracic, intraspinal, and intrasternal injections and infusions.

[0036] As used herein, the term "pharmaceutical composition" refers to an active agent optionally formulated with one or more pharmaceutically acceptable carriers and other additives. In some embodiments, the active agent is present in a unit dosage amount appropriate for administration in a treatment regimen that exhibits a statistically significant probability of achieving a predetermined therapeutic effect when administered to a relevant population. In some embodiments, the pharmaceutical composition may be specially formulated for administration in solid or liquid form, for example, adapted for oral administration, for example, a drain (aqueous or non-aqueous solution or suspension), a tablet, for example, for buccal, sublingual, systemic absorption purposes, a bolus, a powder, a granule, a paste to be applied to the tongue; parenteral administration, for example by subcutaneous, intramuscular, intravenous, epidural injection, for example a sterile solution or suspension, or a sustained release formulation; topical application, for example as a cream, an ointment, or a controlled release patch or spray applied to the skin, the lung, the oral cavity, topical application; intravaginal or rectal, for example as a pessary, a cream, or a foam; sublingual; ocular; transdermal; or nasal, pulmonary, and other mucosal surfaces.

[0037] As used herein, the term "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition, or vehicle such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material involved in carrying or transporting a test compound from one organ or part of the body to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Examples of materials used as pharmaceutically acceptable carriers include the following. Sugars such as lactose, glucose, sucrose; starches such as corn starch and potato starch; cellulose and its derivatives (such as sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate); tragacanth gum powder; malt; gelatin; talc; excipients (such as cocoa butter, suppository waxes); oils (such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil); glycols (such as propylene glycol); polyols (such as glycerin, sorbitol, mannitol, polyethylene glycol); esters (such as ethyl oleate, ethyl laurate); agar; buffering agents (such as magnesium hydroxide and aluminum hydroxide); alginic acid; sterile water; isotonic saline; Ringer's solution; ethyl alcohol; pH buffering solutions; polyesters, polycarbonates, and / or polyanhydrides; and other non-toxic compatible substances used in pharmaceutical formulations.

[0038] As used herein, the terms "subject", "test subject" and related terms refer to any organism to which a provided compound or composition is administered, for example for experimental, diagnostic, prophylactic, and / or therapeutic purposes. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, humans, etc.; fish; birds; insects; nematodes, etc.) and plants. In some embodiments, the subject is suffering from and / or may be susceptible to a disease, disorder, and / or condition. In some embodiments, the subject is a human or other mammal. In some embodiments, the subject may be male or female. By way of non-limiting example, the animal is a vertebrate such as a primate, rodent, livestock or game animal. By way of non-limiting example, primates include chimpanzees, cynomolgus monkeys, rhesus monkeys, macaques (e.g., rhesus macaques), etc. Rodents include mice, rats, woodchucks, ferrets, rabbits, hamsters, etc. By way of non-limiting example, livestock and game animals include cows, horses, pigs, deer, bison, buffalo, felines such as domestic cats, canines such as dogs, foxes, wolves, birds such as chickens, emus, ostriches, fish such as salmon, catfish, trout, etc. In certain embodiments described herein, the subject is a mammal, such as a primate, such as a human. By way of non-limiting example, mammals include humans, non-human primates, mice, rats, dogs, cats, horses, cows, etc., but are not limited thereto. In some embodiments, non-human mammals can be advantageously used as subjects representing animal models of autoimmune diseases or diseases associated with inflammation. In some embodiments, the methods and compositions described herein can be used for the treatment of livestock and / or pets.

[0039] A "therapeutically effective amount" of a composition is an amount sufficient to achieve the desired therapeutic effect and thus does not require a cure or complete remission. In embodiments of the present application, the therapeutic effect is an improvement in any of the disease indicators, and the therapeutically effective amount is sufficient to cause a clinically significant improvement in the condition / symptoms in the treated individual. As used herein, the terms "therapeutically effective amount" and "effective amount" mean an amount sufficient to reduce by at least about 15%, preferably at least about 50%, more preferably at least about 90%, or an amount sufficient to increase by at least about 50%, at least about 100%, at least about 200%, more preferably at least about 500%, and can prevent clinically significant deficiencies in the activity, function, and response of the individual being treated. The effective amount can vary depending on factors such as the physical build and weight of the subject, the type of disease, or the specific agent being applied. For example, the choice of the agent being applied can affect what constitutes an "effective amount". A person of ordinary skill in the art would be able to study the factors included herein and make a determination regarding the effective amount of the agent of the present application without undue experimentation.

[0040] The dosing regime can potentially affect what constitutes an effective amount. The agents of the present application can be administered to a subject either before or after the disease diagnosis or condition. Further, the dosage can be divided into several doses and the doses can be administered daily or continuously, or the dosage can be continuously infused, or can be a bolus injection. Further, the dosage of the agent(s) of the present application can be proportionally increased or decreased as indicated by the urgency of the therapeutic or prophylactic situation.

[0041] As used herein, the terms "treat," "treats," "treating," or "treatment" have the meaning generally understood in the medical arts and thus do not require cure or complete remission and include any beneficial or desired clinical outcome. Non-limiting examples of such beneficial or desired clinical outcomes include an extended lifespan compared to the lifespan expected without treatment, and alleviation of one or more of the following symptoms: weakness and atrophy of proximal skeletal muscle, inability to sit or walk independently, dysphagia, dyspnea, and the like.

[0042] As used herein, "preventing" or "delaying" a disease refers to inhibiting the full onset of the disease.

[0043] This disclosure is based on the unexpected discovery that compounds having certain structures that include a nitrogen-containing five-membered heterocyclic moiety can bind directly or indirectly to at least one oligonucleotide to assist in the delivery of the oligonucleotide to a subject, thereby improving the modulation of a target gene both in vitro and / or in vivo. In an exemplary embodiment, the compounds disclosed herein can significantly enhance oligonucleotide delivery efficiency to the liver by combining endosomal escape and nuclear translocation design without the need for a delivery vector or formulation.

[0044] In an exemplary embodiment, the nitrogen-containing five-membered heterocyclic moiety may have a core structure represented by any of the following formulas, and for the sake of simplicity, all chemical bonds, atoms, and substituents attached to the ring atoms of the core structure are omitted.

[0045]

Chemical formula

[0046]

Chemical formula

[0047] The core structures shown above contain different ring atoms, and the fused ring core structures can be electrically neutral or locally charged, for example, in the form of sulfonium or quaternary ammonium. One or more unsaturated double bonds may move within the fused ring core structure by delocalized π - electron conjugation effects, and all substituents, including in the presence / absence of substituents, can vary depending on the category and valence of each ring atom to which the substituent is attached. For example, additional substituents may be attached to the sulfonium or quaternary ammonium ions present as ring atoms of the fused cyclic core structure. All these variations are within the scope of the concepts of the present disclosure.

[0048] In one embodiment, the compounds of the present disclosure include a structure of formula BI, where X’ is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur, each of F’, G’, H’, and I’ is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur, and each of the asterisks refers to a site that optionally binds directly or indirectly to at least one substituent or oligonucleotide.

[0049]

Chemical formula

[0050] In one embodiment, the compounds of the present disclosure have a structure represented by formula AI or formula AII.

[0051]

Chemical formula

[0052] Here,

[0053]

Chemical formula

[0054] Each independently represents a single or double covalent bond; X is, at each occurrence, an atom selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; each of F, G, H, and I is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur.

[0055] In one embodiment, m is an integer of 1, 2, or 3, n is an integer of 1, 2, or 3, and m + n = 4. In some exemplary embodiments, m = 1 and n = 3, or m = 2 and n = 2, or m = 3 and n = 1.

[0056] In one embodiment, C is, at each occurrence, either absent or selected from the group consisting of hydrogen. A halogen atom such as fluorine, chlorine, bromine, or iodine; hydroxyl; (C1-C 25 )alkyl, for example -(C2-C 22 )alkyl, or -(C2-C 19 )alkyl, or -(C3-C 18 )alkyl, or -(C4-C 16 )alkyl, or -(C6-C 12 )alkyl, or -(C8-C 10 )alkyl; (C1-C 20 )alkoxy, for example -(C2-C 19 )alkoxy, or -(C3-C 18 )alkoxy, or -(C4-C 16 )alkoxy, or -(C6-C 12 )alkoxy; halogenated (C1-C 20 )alkyl, for example halogenated (C2-C19)alkyl, or halogenated (C3-C 18 )alkyl, or halogenated (C4-C16alkyl, or halogenated (C6-C 12 )alkyl, or halogenated (C8-C 10 )alkyl; and halogenated (C1-C 20 )alkoxy, for example halogenated (C2-C 19 )alkoxy, or halogenated (C8-C 10alkoxy, or halogenated (C4-C 16 alkoxy, or halogenated (C6-C 12 ) alkoxy; wherein, "halogenated" can be fluorination, chlorination, bromination, iodination, or a combination thereof. In one embodiment, in the structure represented by Formula I, each B is bonded to any one of F, G, H, and I, and C is bonded to the remaining F, G, H, and I. In one embodiment, B is bonded to H, and the three Cs are each individually bonded to F, G, and I. In another embodiment, B is bonded to G, and the three Cs are each individually bonded to F, H, and I. In another embodiment, B is bonded to F, and the three Cs are each bonded to G, H, I. In another embodiment, B is bonded to I, and the three Cs are each bonded to F, G, H. In another embodiment, two Bs are each bonded to G and H, and two Cs are each bonded to F and I.

[0057] In one embodiment, B is independently selected from the group consisting of hydroxyl at each occurrence. -C(O)OH; -P(O)2-OH; -P(O)-OH; -P(O)(S)-OH; -CN; -(C1-C 22 ) alkyl, for example, -(C2-C 20 ) alkyl, or -(C3-C 16 ) alkyl, or -(C6-C 12 ) alkyl; -O-(C1-C 22 ) alkyl, for example, -O-(C2-C 20 ) alkyl, or -O-(C3-C 16 ) alkyl, or -O-(C6-C 12 ) alkyl; -(C1-C 22 ) alkenyl, for example, -(C2-C 20 ) alkenyl, or -(C3-C 16 ) alkenyl, or -(C6-C 12 ) alkenyl; -(C1-C 22 ) alkylene-OH, for example, -(C2-C 20 ) alkylene-OH, or -(C3-C 16 ) alkylene-OH, or -(C6-C12 ) alkylene-OH; -(C3-C 22 ) cycloalkylene-OH, e.g., -(C5-C 16 ) cycloalkylene-OH, or -(C6-C 12 ) cycloalkylene-OH, or -(C6-C 10 ) cycloalkylene-OH; -(C6-C 22 ) arylene-OH; -(C6-C 22 ) heteroarylene-OH; -(C1-C 22 ) alkylene-C(O)OH, e.g., -(C2-C 18 ) alkylene-C(O)OH, or -(C3-C 16 ) alkylene-C(O)OH, or -(C6-C 12 ) alkylene-C(O)OH; -(C3-C 22 ) cycloalkylene-C(O)OH; -(C6-C 22 ) arylene-C(O)OH; -(C5-C 22 ) heteroarylene-C(O)OH; -O-C(O)-(C1-C 22 ) alkylene-C(O)NH2, e.g., -O-C(O)-(C2-C 18 ) alkylene-C(O)NH2, or -O-C(O)-(C3-C 16 ) alkylene-C(O)NH2, or -O-C(O)-(C6-C 12 ) alkylene-C(O)NH2; -(C1-C 22 ) alkylene-O-C(O)-(C1-C 22 ) alkylene-C(O)NH2, e.g., -(C2-C 18 ) alkylene-O-C(O)-(C2-C 18 ) alkylene-C(O)NH2, or -(C3-C 16 ) alkylene-O-C(O)-(C3-C 16 ) alkylene-C(O)NH2, or -(C6-C 12 ) alkylene-O-C(O)-(C6-C 12 ) alkylene-C(O)NH2; -O-C(O)-(C1-C 22 ) alkylene-C(O)OH; -(C1-C22 )(alkylene)-O-C(O)-(C1-C 22 )(alkylene)-C(O)OH; -C(O)-(C1-C 22 )(alkylene)-C(O)NH2; -(C1-C 22 )(alkylene)-C(O)-(C1-C 22 )(alkylene)-C(O)NH2; -C(O)-NH-(C1-C 22 )(alkylene)-OH; -C(O)-NH-(C1-C 22 )(alkylene)-C(O)OH; -(C1-C 22 )(alkylene)-C(O)-NH-(C1-C 22 )(alkylene)-C(O)OH; -(C1-C 30 )(alkylene)-P(O)2-OH; -(C1-C 22 )(alkylene)-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )(alkylene)-CN, for example, -(C2-C 18 )(alkylene)-O-P(-N(C2-C 18 alkyl)2)-O-(C2-C 18 )(alkylene)-CN, or -(C3-C 16 )(alkylene)-O-P(-N(C3-C 16 alkyl)2)-O-(C3-C 16 )(alkylene)-CN, or -(C6-C 12 )(alkylene)-O-P(-N(C6-C 12 alkyl)2)-O-(C6-C 12 )(alkylene)-CN; -(C1-C 22 )(alkylene)-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )(alkylene)-OH; -(C1-C 22 )(alkylene)-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )(alkylene)-NH2; -(C1-C 22 )(alkylene)-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )(alkylene)-C(O)OH; -C(O)-NH-(C1-C22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-CN; -C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-OH; -C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 30 ) alkylene-C(O)OH; -C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-NH2; -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-CN; -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-OH; -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-C(O)OH; -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-NH2; -(C1-C 22 ) alkylene -P(O)-OH; -(C1-C 22 ) alkylene-P(O)(S)-OH and -(C1-C 22 ) alkylene-CN. Contained in B (C1-C 22)Alkyl or (C1-C 22 )Each of the alkylene groups is alkyl or alkylene containing from 1 to 22 carbon atoms, 2 to 20 carbon atoms, or 3 to 16 carbon atoms, or 4 to 12 carbon atoms, or 6 to 12 carbon atoms, or 8 to 10 carbon atoms consisting of alkyl or alkylene.

[0058] In one embodiment, each of A1, A2, and A3 is a substituent that is absent or independently selected from the group consisting of: -H, -OH, -O-R 1 , -SH, -(C1-C 25 )alkyl, halogenated -(C1-C 25 )alkyl, -(C2-C 22 )alkenyl, -(C1-C 22 )alkylene-OH, -(C3-C 22 )cycloalkyl, -(C3-C 22 )cycloalkenyl, -(C1-C 22 )alkylene-(C3-C 22 )cycloalkyl, -(C1-C 22 )alkylene-R 1 , -(C1-C 22 )alkylene-O-R 1 , -(C1-C 22 )alkylene-COOR 1 , -C(O)O-R 1 ,-O-(C1-C 22 )alkyl, -S-(C1-C 22 )alkyl, -C(O)-R 1 , -C(O)-(C1-C 22 )alkyl, -O-C(O)-(C1-C 22 )alkyl, -O-C(O)-R 1 , -(C1-C 22 )alkylene-O-C(O)-R 1 , -C(O)-(C1-C 22 )alkylene-OH, -C(O)-(C1-C 22 )alkylene-R 1 , -C(O)-(C1-C 22Alkylene-NH-R 1 , -C(O)-(C1-C 22 )Alkylene-NR 2 -R 1 , -O-C(O)-(C1-C 22 )Alkylene-OH, -O-C(O)-(C1-C 22 )Alkylene-R 1 , -Adamantyl, -(C1-C 22 )Alkylene-Adamantyl, -O-Adamantyl,-C(O)-(C1-C 22 )Alkylene-Adamantyl, -(C1-C 22 )Alkylene-C(O)-(C1-C 22 )Alkylene-Adamantyl, -NH-C(O)-(C1-C 22 )Alkylene-Adamantyl, -(C1-C 22 )Alkylene-NH-C(O)-(C1-C 22 )Alkyl, -(C1-C 22 )Alkylene-NH-C(O)-Halogenated (C1-C 22 )Alkyl, -CH(NH-CO-(C1-C 22 )Alkyl)-(C1-C 22 )Alkylene-NH-C(O)-(C1-C 22 )Alkyl, -C(O)-(C1-C 22 )Alkylene-C(O)-NH-C[-(C1-C 22 )Alkylene-O-(C1-C 22 )Alkylene-C(O)-NH-(C1-C 22 )Alkylene-NH-C(O)-(C1-C 22 )Alkyl]3, -C(O)-(C1-C 22 )Alkylene-C(O)-NH-C[-(C1-C 22 )Alkylene-O-(C1-C 22 )Alkylene-C(O)-NH-(C1-C 22 )Alkylene-NH-C(O)-(C1-C 22 )Alkylene-R 1 3, -CH(NH-CO-Halogenated (C1-C 22 )Alkyl)-(C1-C 22) Alkylene-NH-C(O)-halogenated (C1-C 22 ) Alkyl, -(C1-C 22 ) Alkylene-NH-C(O)-(C1-C 22 ) Alkylene-adamantyl, -(C1-C 22 ) Alkylene-NR 2 -C(O)-(C1-C 22 ) Alkylene-adamantyl, -(C1-C 22 ) Alkylene-(C1-C6 alkylene oxide) (1-20) -NH-C(O)-(C1-C 22 ) Alkylene-adamantyl, -C(O)NH-(C1-C 22 ) Alkyl, -C(O)NH-R 1 , -C(O)NR 2 -R 1 , -C(O)NH-(C1-C 22 ) Alkylene-OH, -C(O)NH-(C1-C 22 ) Alkylene-COOH, -NH-C(O)-(C1-C 22 ) Alkyl, -NH-C(O)-R 1 , -NR 2 -C(O)-R 1 , -O-P(O)2-O-R 1 ,-OP(O)(S)-O-R 1 ,-O-P(O)-O-R 1 , -NH-R 1 , -NR 2 -R 1 ,-(C1-C 22 ) Alkylene-NH-R 1 , -(C1-C 22 ) Alkylene-NR 2 -R 1 , -C(O)-(C1-C 22 ) Alkylene-C(O)-R 1 , -C(O)-(C1-C 22 ) Alkylene-C(O)O-R 1 , -C(O)-(C1-C 22 ) Alkylene-NH-C(O)-R 1 , -C(O)-(C1-C 22 ) Alkylene-NR 2-C(O)-R 1 , -(C1-C 22 ) alkylene-C(O)-R 1 , -(C1-C 22 ) alkylene-NH-C(O)-R 1 , -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-C(O)- NH-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-NR 2 -C(O)-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-CN, -(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-OH, -(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-NH2, -(C1-C 22 ) alkylene-O-P(-N(C1-C 22(Alkyl)2)-O-(C1-C 22 ) alkylene - C(O)OH, -C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 22 ) alkylene - CN, -C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 22 ) alkylene - OH, -C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 30 ) alkylene - C(O)OH, -C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 22 ) alkylene - NH2, -(C1-C 22 ) alkylene - C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 22 ) alkylene - CN, -(C1-C 22 ) alkylene - C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 22 ) alkylene - OH, -(C1-C 22 ) alkylene - C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 22 ) alkylene - C(O)OH, -(C1-C 22 ) alkylene - C(O)-NH-(C1-C 22 ) alkylene - O - P(-N(C1-C 22 (Alkyl)2)-O-(C1-C 22 ) alkylene - NH2, -(C1-C 22 ) alkylene - P(O)-OH, -(C1-C 22) Alkylene - P(O)(S) - OH, -(C1 - C 22 ) Alkylene - CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzothiazole, where when the rings shown above are substituted, the substituents are hydroxyl group, halogen atom (such as fluorine, chlorine, bromine, iodine, etc.), (C1 - C 16 ) alkyl, (C1 - C 16 ) alkoxy, and also include the substituents represented by formula III.

[0059]

Chemical formula

[0060] In one embodiment, each of R3, R4, and R5 is either absent or a substituent independently selected from the group consisting of -H, -OH, -O - R 1 , -SH, -(C1 - C 25 ) alkyl, halogenated -(C1 - C 25 ) alkyl, -(C2 - C 22 ) alkenyl, -(C1 - C 22 ) alkylene - OH, -(C3 - C 22 ) cycloalkyl, -(C3 - C 22 ) cycloalkenyl, -(C1 - C22 ) alkylene-(C3-C 22 ) cycloalkyl, -(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-O-R 1 , -(C1-C 22 ) alkylene-COOR 1 , -C(O)O-R 1 ,-O-(C1-C 22 ) alkyl, -S-(C1-C 22 ) alkyl, -C(O)-R 1 , -C(O)-(C1-C 22 ) alkyl, -O-C(O)-(C1-C 22 ) alkyl, -O-C(O)-R 1 , -(C1-C 22 ) alkylene-O-C(O)-R 1 , -C(O)-(C1-C 22 ) alkylene-OH, -C(O)-(C1-C 22 ) alkylene-R 1 , -C(O)-(C1-C 22 ) alkylene-NH-R 1 , -C(O)-(C1-C 22 ) alkylene-NR 2 -R 1 , -O-C(O)-(C1-C 22 ) alkylene-OH, -O-C(O)-(C1-C 22 ) alkylene-R 1 , -adamantyl, -(C1-C 22 ) alkylene-adamantyl, -O-adamantyl,-C(O)-(C1-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-C(O)-(C1-C 22 ) alkylene-adamantyl, -NH-C(O)-(C1-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkyl, -(C1-C 22 ) alkylene-NH-C(O)-halogenated (C1-C22 ) alkyl, -CH(NH-CO-(C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkyl, -C(O)-(C1-C 22 ) alkylene-C(O)-NH-C[-(C1-C 22 ) alkylene-O-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkyl]3, -C(O)-(C1-C 22 ) alkylene-C(O)-NH-C[-(C1-C 22 ) alkylene-O-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-R 1 3, -CH(NH-CO-halogenated (C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-NH-C(O)-halogenated (C1-C 22 ) alkyl, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-NR 2 -C(O)-(C1-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-(C1-C6 alkylene oxide) (1-20) -NH-C(O)-(C1-C 22 ) alkylene-adamantyl, -C(O)NH-(C1-C 22 ) alkyl, -C(O)NH-R 1 , -C(O)NR 2 -R 1 , -C(O)NH-(C1-C 22 ) alkylene-OH, -C(O)NH-(C1-C 22 ) alkylene-COOH, -NH-C(O)-(C1-C 22Alkyl, -NH-C(O)-R 1 , -NR 2 -C(O)-R 1 , -O-P(O)2-O-R 1 ,-OP(O)(S)-O-R 1 ,-O-P(O)-O-R 1 , -NH-R 1 , -NR 2 -R 1 ,-(C1-C 22 ) Alkylene-NH-R 1 , -(C1-C 22 ) Alkylene-NR 2 -R 1 , -C(O)-(C1-C 22 ) Alkylene-C(O)-R 1 , -C(O)-(C1-C 22 ) Alkylene-C(O)O-R 1 , -C(O)-(C1-C 22 ) Alkylene-NH-C(O)-R 1 , -C(O)-(C1-C 22 ) Alkylene-NR 2 -C(O)-R 1 , -(C1-C 22 ) Alkylene-C(O)-R 1 , -(C1-C 22 ) Alkylene-NH-C(O)-R 1 , -(C1-C 22 ) Alkylene-NH-C(O)-(C1-C 22 ) Alkylene-R 1 , -(C1-C 22 ) Alkylene-NH-C(O)-(C1-C 22 ) Alkylene-NH-C(O)-(C1-C 22 ) Alkylene-R 1 , -(C1-C 22 ) Alkylene-C(O)-NH-(C1-C 22 ) Alkylene-R 1 , -(C1-C 22 ) Alkylene-C(O)- NH-(C1-C 22 ) Alkylene-C(O)-NH-(C1-C 22 ) Alkylene-R 1, -(C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - NH - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - NR 2 - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - CN, -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - OH, -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - NH2, -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - C(O)OH, -C(O) - NH - (C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - CN, -C(O) - NH - (C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - OH, -C(O) - NH - (C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 30 ) alkylene - C(O)OH, -C(O) - NH - (C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - NH2, -(C1-C 22 ) alkylene - C(O) - NH - (C1-C22 ) Alkylene - O - P(-N(C1 - C 22 ) alkyl)2)-O-(C1 - C 22 ) Alkylene - CN, -(C1 - C 22 ) Alkylene - C(O)-NH-(C1 - C 22 ) Alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) Alkylene - OH, -(C1 - C 22 ) Alkylene - C(O)-NH-(C1 - C 22 ) Alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) Alkylene - C(O)OH, -(C1 - C 22 ) Alkylene - C(O)-NH-(C1 - C 22 ) Alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) Alkylene - NH2, -(C1 - C 22 ) Alkylene - P(O)-OH, -(C1 - C 22 ) Alkylene - P(O)(S)-OH,-(C1 - C 22 ) Alkylene - CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, and substituted or unsubstituted benzothiazole, where, when the rings shown above are substituted, the substituents may include a hydroxyl group, a halogen atom (such as fluorine, chlorine, bromine, iodine, etc.), (C1 - C 16 ) alkyl, (C1 - C 12 ) alkoxy.

[0061] In one embodiment, R 7 is, in each occurrence, bonded to any one of P, Q, S, and T and is selected from the group consisting of hydrogen, a halogen atom, hydroxyl, (C1-C 20 )alkyl, (C1-C 20 )alkoxy, halogenated (C1-C 20 )alkyl, and halogenated (C1-C 20 )alkoxy, or is not included in that group.

[0062] In one embodiment, M is an integer of 0, 1, 2, or 3.

[0063] In one embodiment, R 6 is bonded to any one of P, Q, S, T and is selected from the group consisting of a direct bond. -O-, -C(O)O-, -O-C(O)-, -P(O)2-O-, -O-P(O)2-O-, -P(O)(S)-O-, -O-P(O)(S)-O-, -O-P(O)-O-, -(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-O-, -O-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-, -NH-(C1-C 22 )alkylene-, -C(O)-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-C(O)-, -C(O)-O-(C1-C 22 )alkylene-, -(C1-C 30 )alkylene-C(O)-O-, -C(O)-NH-(C1-C 22 )alkylene-, -C(O)-NH-(C1-C 22 )alkylene-C(O)-O-, -C(O)-NH-(C1-C 22 )alkylene-O-C(O)-, -C(O)-NH-(C1-C 22 )alkylene-O-C(O)-O-, -C(O)-NH-(C1-C 22 )alkylene-O-, -C(O)-N((C1-C 22 )alkyl)-(C1-C 22) alkylene-, -C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-O-, -C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-, -C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-, -C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-, -C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-, -C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-C(O)-N((C1-C 22 ) alkyl)-, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-, -NH-C(O)-(C1-C 22 ) alkylene-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-O-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-O-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-O-, -NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-, -NH-C(O)-(C1-C 22) alkylene-NH-C(O)-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-N((C1-C 22 ) alkyl)-C(O)-, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-, -(C1-C 22 ) alkylene -P(O)2-O-, -(C1-C 22 ) alkylene-O-P(O)2-O-, -(C3-C 22 ) cycloalkylene-, -(C3-C 22 ) cycloalkylene-O-, -O-(C3-C 22 ) cycloalkylene-, -(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-O-, -O-(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-NH-, -NH-(C6-C 22 ) arylene-, -C(O)-(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-C(O)-, -C(O)-O-(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-C(O)-O-, -C(O)-NH-(C6-C 22 ) arylene- and -C(O)-NH-(C6-C 22 ) arylene-C(O)-O-.

[0064] In one embodiment, in each occurrence, R1 is independently selected from the group consisting of the following. Hydrogen, hydroxyl, -(C1-C 22 ) alkyl, -(C3-C 22 ) cycloalkyl, -(C6-C 22 ) aryl, -(C1-C 22 ) alkoxy, -(C3-C 22 ) cycloalkoxy, -(C6-C 22 ) aryloxy, -C(O)-(C1-C 22 ) alkyl, -OC(O)(C1-C 22 ) alkyl, -C(O)-O-(C1-C 22 ) alkyl, -C(O)-(C3-C 22 ) cycloalkyl, -OC(O)-(C3-C 22 ) cycloalkyl, -C(O)-O-(C3-C 22 ) cycloalkyl, -C(O)-(C6-C 22 ) aryloxy, -OC(O)-(C6-C 22 ) aryloxy, -C(O)-O-(C6-C 22 ) aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, glucosyl, acetamidoglucosyl, acetylglucosamine, lipid, PEG, steroid, lipophilic substance, carbohydrate, cholesterol, adamantane, amino acid, peptide, chloroquine and alkaloid.

[0065] In one embodiment, R 2 is, in each occurrence, independently selected from the group consisting of a halogen atom, (C1-C 12 ) alkyl, (C1-C 12 ) alkoxy, (C1-C 12 ) alkoxycarbonyl, (C6-C 16 ) aryl, or (C6-C 16 ) aryloxycarbonyl.

[0066] In one embodiment, A1, A2, A3, B, C, R 1 、R 2 、R 3 、R4 and R 5 and R 7 One or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in R can be protected with a terminal protecting group R selected from the group consisting of P . (C1-C 22 ) alkyl, (C1-C 22 ) alkoxy, (C1-C 22 ) alkylcarbonyl, (C1-C 22 ) alkoxycarbonyl, (C6-C 22 ) aryl, (C6-C 22 ) aryloxy, (C6-C 22 ) arylcarbonyl, (C6-C 22 ) aryloxycarbonyl, tri((C1-C 22 ) alkyl)silyl, and tri((C1-C 22 ) alkoxy)silyl, where the (C1-C P ) alkyl contained in the protecting group R 22 can be alkyl containing from 1 to 22 carbon atoms, such as alkyl containing from 2 to 20 carbon atoms, or from 3 to 18 carbon atoms, or from 4 to 16 carbon atoms, or from 6 to 12 carbon atoms. The (C1-C 22 ) alkoxy contained in Rp can be alkoxy containing from 1 to 22 carbon atoms, such as alkoxy containing from 2 to 20 carbon atoms, or from 3 to 18 carbon atoms, or from 4 to 16 carbon atoms, or from 6 to 12 carbon atoms. The (C6-C 22 ) aryl contained in Rp can be aryl containing from 6 to 22 carbon atoms, such as aryl containing from 6 to 20 carbon atoms, or from 6 to 18 carbon atoms, or from 6 to 16 carbon atoms, or from 6 to 12 carbon atoms, or from 8 to 10 carbon atoms. Also, the (C6-C 22 ) aryloxy contained in Rp can be aryloxy containing from 6 to 22 carbon atoms, and can be, for example, aryloxy containing from 6 to 20 carbon atoms, from 6 to 18 carbon atoms, from 6 to 16 carbon atoms, from 6 to 12 carbon atoms, or from 8 to 10 carbon atoms.

[0067] In one embodiment, A1, A2, and A3 are not hydrogen at the same time, and R 3 , R 4 , and R 5 are not hydrogen at the same time. In an exemplary embodiment, X is carbon and all of A1, A2, and A3 are present. In another embodiment, X is nitrogen, both A1 and A2 are present, and A3 is not present. In another embodiment, X is nitrogen having a positive charge (i.e., quaternary ammonium), and all of A1, A2, and A3 are present. In another embodiment, X is sulfur or oxygen, A1 and A3 are not present, and A2 is present. In another embodiment, X is sulfur having a positive charge (i.e., sulfonium), A2 and A3 are present, and A1 is not present.

[0068] In one embodiment, each of the (C1-C22) alkyl or (C1-C22) alkylene included in A1, A2, A3, B, C, R 1 , R 2 , R 3 , R 4 , R 5 , and R 7 is alkyl or alkylene consisting of 1 to 22 carbon atoms, or 2 to 20 carbon atoms, or 3 to 16 carbon atoms, or 4 to 12 carbon atoms, or 6 to 12 carbon atoms, or 8 to 10 carbon atoms.

[0069] In one embodiment, one or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups included in A1, A2, A3, B, C, R 1 , R 2 , R 3 , R 4 , R 5 , and R 7 can bind to a support material selected from the group consisting of silica, silica gel, glass, ceramic, polymer, cellulose, and combinations thereof. In some embodiments, the solid material is in the form of beads. These beads can be made of any material such as magnetic beads, paramagnetic beads, silica beads, agarose beads, etc.

[0070] In another embodiment, the compounds of the present disclosure may have a structure represented by any of Formula AIV to Formula AXV.

[0071]

Chem.

[0072] Here, A1’, A2’, and A3, B, C, F, G, H, I, m and n are as defined above.

[0073] In one embodiment, the compounds of the present disclosure have a structure represented by Formula BII.

[0074]

Chem.

[0075] Here, X’ is selected from the group consisting of carbon, nitrogen, oxygen and sulfur, and each of F’, G’, H’ and I’ is independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur.

[0076] In another embodiment, each of A1’, A2’, and A3 is either absent or a substituent independently selected from the group consisting of -H, -R 1 ’, -O-R 1 ’, -S-R 1 ’, -C(O)-R 1 ’, -C(O)O-R 1 ’, -O-C(O)-R 1 ’, -C(O)NH-R 1 ’, -C(O)NR 2 ’-R 1 ’, -NH-C(O)-R 1 ’, -NR 2 ’-C(O)-R 1 ’, -O-P(O)2-O-R 1 ’, -OP(O)(S)-O-R 1 ’, -O-P(O)-O-R 1 ’, -NH-R1 ’, -NR 2 ’-R 1 ’, -(CH2) r’ -NH-R 1 ’, -(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -R 1 ’, -C(O)-(CH2) r’ -NH-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -C(O)-R 1 ’, -C(O)-(CH2) r’ -C(O)O-R 1 ’, -C(O)-(CH2) r’ -NH-C(O)-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-C(O)-R 1 ’, -(CH2) r’ -C(O)-R 1 ’; -(CH2) r’ -C(O)O-R 1 ’; -(CH2) r’ -O-C(O)-R 1 ’, -(CH2) r’ -R 1 ’, -(CH2) r’ -NH-C(O)-R 1 ’, -(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’, -(CH2) r’ -NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-(CH2) s’ -R 1 ’, -(CH2) r’ -C(O)-NH-(CH2) s’ -R 1 ’, -(CH2) r’ -C(O)-NH-(C1-C 22)Alkylene-C(O)-NH-(CH2) s’ -R 1 ’, -(CH2) r’ -C(O)-NH-(C1-C 22 )Alkylene-NH-C(O)-(CH2) s’ -R 1 ’, -(CH2) r’ -NR 2 ’-C(O)-(CH2) s’ -R 1 ’, -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -C(O)-NH-(CH2) s’ -R 1 ’)(-C(O)-NH-(CH2) q’ -R 3 ’), -N(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’-NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), or A1’ and A2’ may combine to form an unsubstituted or substituted heterocyclic ring with A1’, A2’, the nitrogen atom bonded to A1’, and the carbon atom bonded to A2’. Each (C1-C 22 ) alkylene contained in A1’, A2’ and A3’ can be (C2-C 20 ) alkylene, (C3-C 16 ) alkylene, (C4-C 14 c) alkylene, (C6-C 12 ) alkylene, or (C8-C 10 ) alkylene. R1’ and R3’ are each independently selected from the group consisting of the following. Hydrogen; hydroxyl; (C1-C 30 ) alkyl, for example -(C2-C 25 ) alkyl, or -(C2-C22 ) alkyl, or -(C3-C 18 ) alkyl, or -(C4-C 16 ) alkyl, or -(C6-C 12 ) alkyl, or -(C8-C 10 ) alkyl; -(C3-C 50 ) cycloalkyl, e.g., -(C4-C 40 ) cycloalkyl, or -(C5-C 30 ) cycloalkyl, or -(C6-C 20 ) cycloalkyl, or -(C6-C 16 ) cycloalkyl; -(C6-C 50 ) aryl, e.g., -(C6-C 40 ) aryl, or -(C6-C 30 ) aryl, or -(C6-C 25 ) aryl, or -(C6-C 22 ) aryl, or -(C6-C 16 ) aryl, or -(C6-C 12 ) aryl; -(C1-C 30 ) alkoxy, e.g., -(C2-C 22 ) alkoxy, or -(C3-C 20 ) alkoxy, or -(C4-C 16 ) alkoxy, or -(C6-C 12 ) alkoxy; -(C3-C 50 ) cycloalkoxy, e.g., -(C4-C 40 ) cycloalkoxy, or -(C5-C 30 ) cycloalkoxy, or -(C6-C 20 ) cycloalkoxy, or -(C6-C 16 ) cycloalkoxy; -(C6-C 50 ) allyloxy, e.g., -(C6-C 40 ) allyloxy, or -(C6-C 30 ) allyloxy, or -(C6-C 25 ) allyloxy, or -(C6-C 22 ) allyloxy, or -(C6-C 16 ) allyloxy, or -(C6-C12 )allyloxy; -C(O)-(C1-C 30 )alkyl, e.g., -C(O)-(C2-C 22 )alkyl, or -C(O)-(C3-C 18 )alkyl, or -C(O)-(C4-C 16 )alkyl, or -C(O)-(C6-C 12 )alkyl, or -C(O)-(C8-C 10 )alkyl; -OC(O)(C1-C 30 )alkyl, e.g., -OC(O)(C2-C 22 )alkyl, or -OC(O)(C3-C 18 )alkyl, or -OC(O)(C4-C 16 )alkyl, or -OC(O)(C6-C 12 )alkyl, or -OC(O)(C8-C 10 )alkyl; -C(O)-O-(C1-C 30 )alkyl, e.g., -C(O)-O-(C2-C 22 )alkyl, or -C(O)-O-(C3-C 18 )alkyl, or -C(O)-O-(C4-C 16 )alkyl, or -C(O)-O-(C6-C 12 )alkyl, or -C(O)-O-(C8-C 10 )alkyl; -C(O)-(C3-C 50 )cycloalkyl, e.g., -C(O)-(C4-C 40 )cycloalkyl, or -C(O)-(C5-C 30 )cycloalkyl, or -C(O)-(C6-C 20 )cycloalkyl, or -C(O)-(C6-C 16 )cycloalkyl; -OC(O)-(C3-C 50 )cycloalkyl, e.g., -OC(O)-(C4-C 40 )cycloalkyl, or -OC(O)-(C5-C 30 )cycloalkyl, or -OC(O)-(C6-C 20 )cycloalkyl, or -OC(O)-(C6-C 16)Cycloalkyl; -C(O)-O-(C3-C 50 )Cycloalkyl, for example -C(O)-O-(C4-C 40 )Cycloalkyl, or -C(O)-O-(C5-C 30 )Cycloalkyl, or -C(O)-O-(C6-C 20 )Cycloalkyl, or -C(O)-O-(C6-C 16 )Cycloalkyl; -C(O)-(C6-C 50 )Allyloxy, for example -C(O)-(C6-C 40 )Allyloxy, or -C(O)-(C6-C 30 )Allyloxy, or -C(O)-(C6-C 25 ) Allyloxy, or -C(O)-(C6-C 22 )Allyloxy, or -C(O)-(C6-C 16 )Allyloxy, or -C(O)-(C6-C 12 )Allyloxy; -OC(O)-(C6-C 50 )Allyloxy, for example -OC(O)-(C6-C 40 )Allyloxy, or -OC(O)-(C6-C 30 )Allyloxy, or -OC(O)-(C6-C 25 ) Allyloxy, or -OC(O)-(C6-C 22 )Allyloxy, or -OC(O)-(C6-C 16 )Allyloxy, or -OC(O)-(C6-C 12 )Allyloxy; -C(O)-O-(C6-C 50 )Allyloxy, for example -C(O)-O-(C6-C 40 )Allyloxy, or -C(O)-O-(C6-C 30 )Allyloxy, or -C(O)-O-(C6-C 25 ) Allyloxy, or -C(O)-O-(C6-C 22 )Allyloxy, or -C(O)-O-(C6-C 16 )Allyloxy, or -(C6-C 12allyloxy; C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, glucosyl, N-acetylglucosyl, N-acetylgalactosamine, lipid, PEG, steroid, lipophilic, carbohydrate, cholesterol, adamantane, amino acid, peptide, ligand, nucleic acid, oligonucleotide oligonucleotide, aptamer, small molecule, antibody, antibody fragment, chloroquine, alkaloid, and a target site described herein.

[0077] In some embodiments, one or more of the substituents A1′, A2′, and A3′ comprise at least one targeting moiety. As used herein, the term “targeting moiety” refers to a portion or segment of a molecule that acts as a chemical signal that binds to a molecule or complex in a particular region of a cell, tissue, or organ. Generally, the targeting moiety modifies one or more properties of the conjugated oligonucleotide of the invention, including but not limited to pharmacodynamics, pharmacokinetics, binding, absorption, cellular distribution, cellular uptake, charge, and clearance. Targeting moieties are routinely used in the art and are attached directly or via any linker moiety to a parent compound such as an oligomeric compound.

[0078] In a particular embodiment, the targeting moiety is selected from ligands, peptides, nucleic acids, oligonucleotides, aptamers, small molecules, polyethylene glycol, amino acids, cholesterol, carbohydrates (such as glucose, galactosamine or N-acetylgalactosamine), antibodies or antibody fragments, and localization signals such as nuclear localization signals or mitochondrial localization signals. In a particular embodiment, the targeting moiety is selected from the group consisting of intercalators, reporter molecules, polyamines, polyamides, vitamin moieties, polyethylene glycol, thioethers, polyethers, thiocolesterol, cholate moieties, folic acid, lipids, fatty acids, phospholipids, biotin, phenazines, phenanthridines, anthraquinones, adamantanes, acridines, fluoresceins, rhodamines, coumarins, fluorescent dyes, fluorescent proteins and dyes. When the target site is a fluorescent substance, all fluorescent substances considered useful can be utilized. Examples of useful fluorescent proteins include, but are not limited to, GFP, EBFP, Azurite, Cerulean, mCFP, Turquoise, ECFP, mKeima-Red, TagCFP, AmCyan, mTFP, TurboGFP, TagGFP, EGFP, TagYFP, EYFP, Topaz, Venus, mCitrine, TurboYFP, mOrange, TurboRFP, tdTomato, TagRFP, dsRed2, mRFP, mCherry, mPlum, mRaspberry, mScarlet, etc. Examples of luminescent proteins include, but are not limited to, Cypridinia luciferase, Gaussia luciferase, Renilla luciferase, Phontinus luciferase, Luciola luciferase, Pyrophorus luciferase, Phrixothrix luciferase, etc.

[0079] In certain embodiments, the targeting moiety is selected from cell-penetrating peptides, polyethylene glycol, alkaloids, tryptamines, benzimidazoles, quinolones, amino acids, cholesterol, carbohydrates, and ligands.

[0080] In one embodiment, the targeting moiety is a carbohydrate. The carbohydrate can be selected from the group consisting of monosaccharides, disaccharides, trisaccharides, and polysaccharides. In some embodiments, the carbohydrate is a monosaccharide selected from the group consisting of glucose, galactose, mannose, mannitol, D-mannose, sorbitol, and sorbose. In another embodiment, the carbohydrate is a disaccharide selected from the group consisting of lactose, maltose, sucrose, and trehalose. In one embodiment, the targeting moiety is a polysaccharide. In one embodiment, the targeting moiety is N-acetylgalactosamine.

[0081] In another embodiment, the targeting moiety is an amino acid. In one embodiment, the amino acid is a hydrophobic amino acid. In some embodiments, the hydrophobic amino acid is selected from the group consisting of alanine, isoleucine, leucine, methionine, phenylalanine, proline, tryptophan, and valine. In yet another embodiment, the amino acid is a polar amino acid. In some embodiments, the amino acid is selected from the group consisting of arginine, histidine, lysine, cysteine, glycine, glutamine, serine, threonine, tyrosine, aspartic acid, and glutamic acid.

[0082] In one embodiment, the targeting moiety is selected from the group consisting of human serum albumin, α-lactalbumin, trypsinogen, and polyalanine.

[0083] In a particular embodiment, the targeting moiety comprises an active pharmaceutical substance. For example, aspirin, warfarin, phenylbutazone, ibuprofen, suprofen, fenbufen, ketoprofen, (S)-(+)-pranoprofen, carprofen, dansylsarcosine, 2,3,5-triiodobenzoic acid, fingolimod, flufenamic acid, folic acid, benzothiadiazole, chlorothiazide, diazepine, indomethacin, barbituric acid, cephalosporin, sulfonamide, antidiabetic agent, antibacterial agent or antibiotic.

[0084] The targeting moieties disclosed herein can be used to increase, introduce, deliver, and target the uptake of oligonucleotides into specific cell or tissue types, such as cells or tissues in the central nervous system (e.g., brain and spinal cord), liver, lung, kidney, intestine, pancreas, gallbladder, heart, lymph nodes, spleen, stomach, bladder, muscle, and bone. Preferred targeting moieties include those specifically described in the examples.

[0085] In one embodiment, at least one of R 1 ’ and R 3 ’ is a targeting moiety. In one embodiment, all of the R 1 ’s included in A1’, A2’, A3’ are the above-described target molecules.

[0086] In another embodiment, all of the R 3 ’s included in A1’, A2’, A3’ are the above-described target molecules.

[0087] In one embodiment, all of the R 1 ’ and R 3 ’s included in A1’, A2’, A3’ are the above-described target molecules.

[0088] In some embodiments, one or more hydroxyl, carboxyl, and amino groups included in each of R1' and R3' can be optionally protected with a terminal protecting group RP selected, for example, from the group consisting of (C1-C 22 ) alkyl, (C1-C 22 ) alkoxy, (C1-C 22 ) alkylcarbonyl, (C1-C 22 ) alkoxycarbonyl, (C6-C 22 ) aryl, (C6-C 22 ) aryloxy, (C6-C 22 ) arylcarbonyl, (C6-C 22 ) aryloxycarbonyl, tri((C1-C 22 ) alkyl)silyl, and tri((C1-C 22 ) alkoxy)silyl, where the (C1-C22 ) The alkyl can be an alkyl containing from 1 to 22 carbon atoms, such as an alkyl containing from 2 to 20 carbon atoms, or from 3 to 18 carbon atoms, or from 4 to 16 carbon atoms, or from 6 to 12 carbon atoms. Rp contains (C1-C 22 ) The alkoxy can be an alkoxy containing from 1 to 22 carbon atoms, such as an alkoxy containing from 2 to 20 carbon atoms, or from 3 to 18 carbon atoms, or from 4 to 16 carbon atoms, or from 6 to 12 carbon atoms. Rp contains (C6-C 22 ) The aryl can be an aryl containing from 6 to 22 carbon atoms, such as an aryl containing from 6 to 20 carbon atoms, or from 6 to 18 carbon atoms, or from 6 to 16 carbon atoms, or from 6 to 12 carbon atoms, or from 8 to 10 carbon atoms. Also, Rp contains (C6-C 22 ) The aryloxy can be an aryloxy containing from 6 to 22 carbon atoms, and can be, for example, an aryloxy containing from 6 to 20 carbon atoms, from 6 to 18 carbon atoms, from 6 to 16 carbon atoms, from 6 to 12 carbon atoms, or from 8 to 10 carbon atoms.

[0089] In some embodiments, each of R2', R4', R5' and R6' is independently a halogen atom such as fluorine, chlorine, bromine or iodine. a (C1-C 12 ) alkyl, such as (C1-C 10 ) alkyl, or (C2-C8) alkyl, or (C3-C6) alkyl, or (C4-C5) alkyl; a (C1-C 12 ) alkoxy, such as (C1-C 10 ) alkoxy, or (C2-C8) alkoxy, or (C3-C6) alkoxy, or (C4-C5) alkoxy; (C1-C 12 ) alkoxycarbonyl, such as (C1-C 10 ) alkoxycarbonyl, or (C2-C8) alkoxycarbonyl, or (C3-C6) alkoxycarbonyl, or (C4-C5) alkoxycarbonyl; (C6-C 16 ) aryl, such as -(C6-C 12)Aryl, or -(C6-C 10 )aryl; or (C6-C 16 )aryloxycarbonyl, e.g., (C6-C 12 )aryloxycarbonyl, or (C6-C 10 )aryloxycarbonyl, or (C6-C8)aryloxycarbonyl.

[0090] In some embodiments, each of r’, s’, p’, q’ is an integer from 1 to 22, such as an integer from 2 to 20, or an integer from 3 to 18, an integer from 4 to 16, an integer from 6 to 12, or an integer from 8 to 10.

[0091] In another embodiment, when X’ is oxygen, A3’ is absent and A1’, A2’ and A3’ are not hydrogen simultaneously. In an exemplary embodiment, X’ is carbon and all of A1’, A2’ and A3’ are present. In another embodiment, X’ is nitrogen, both A1’ and A2’ are present and A3’ is absent. In another embodiment, X’ is nitrogen having a positive charge (i.e., quaternary ammonium) and all of A1’, A2’, A3’ are present. In another embodiment, X’ is sulfur or oxygen, A1’ and A3’ are absent and A2’ is present. In another embodiment, X’ is sulfur having a positive charge (i.e., sulfonium), A2’ and A3’ are present and A1’ is absent.

[0092] In another embodiment, each C’ is bonded to any of F’, G’, H’, I’ and is either absent or selected from the group consisting of the following. Hydrogen; a halogen atom such as fluorine, chlorine, bromine or iodine; hydroxyl; -(C1-C 20 )alkyl, e.g., -(C2-C 19 )alkyl, or -(C3-C 18 )alkyl, or -(C4-C 16 )alkyl, or -(C6-C 12 )alkyl, or -(C8-C 10 )alkyl; (C1-C 20 )alkoxy, e.g., -(C2-C19 ) alkoxy, or -(C3-C 18 ) alkoxy, or -(C4-C 16 ) alkoxy, or -(C6-C 12 ) alkoxy; halogenated (C1-C 20 ) alkyl, for example halogenated (C2-C 19 ) alkyl, or halogenated (C3-C 18 ) alkyl, or halogenated (C4-C 16 ) alkyl, or halogenated (C6-C 12 ) alkyl, or halogenated (C8-C 10 ) alkyl; and halogenated (C1-C 20 ) alkoxy, for example halogenated (C1-C 20 ) alkoxy, halogenated (C2-C 19 ) alkoxy, or halogenated (C3-C 18 ) alkoxy, or halogenated (C4-C 16 ) alkoxy, or halogenated (C6-C 12 ) alkoxy, or halogenated (C8-C 10 ) alkoxy; wherein "halogenated" can be fluorination, chlorination, bromination, iodination, or a combination thereof.

[0093] In one embodiment, m' is an integer of 1, 2 or 3, n' is an integer of 1, 2 or 3, and m'+n' = 4. In some exemplary embodiments, m' = 1 and n' = 3, or m' = 2 and n' = 2, or m' = 3 and n' = 1.

[0094] In one embodiment, each B’ is coupled to any one of F’, G’, H’, I’, and C’ is coupled to the remaining portions of F’, G’, H’, I’. In one embodiment, B’ is coupled to H’, and the three Cs are each individually coupled to F’, G’, I’. In another embodiment, B’ is coupled to G’, and the three Cs are each individually coupled to F’, H’, I’. In another embodiment, B’ is coupled to F’, and the three Cs are each individually coupled to G’, H’, I’. In another embodiment, B’ is coupled to I, and the three Cs are each individually coupled to F’, G’, H’. In another embodiment, two Bs are each coupled to G’ and H’, and two Cs are each individually coupled to F’ and I’.

[0095] In another embodiment, each of the B’s is independently selected from the group consisting of hydroxyl, -C(O)OH, -(C1-C 30 ) alkoxy, -P(O)2-OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C1-C 30 ) alkylene-OH, -(C3-C 50 ) cycloalkylene-OH, -(C6-C 50 ) arylene-OH, -C(O)-NH-[(C1-C 30 ) alkylene-O] r’ -H (where r’ is an integer from 1 to 22), -C(O)-NH-[(C1-C 30 ) alkylene-O] r’ -(C1-C 30 ) alkylene-C(O)-OH (where r’ is an integer from 1 to 22), -(C5-C 50 ) heteroarylene-OH, -(C1-C 30 ) alkylene-C(O)OH, -(C3-C 50 ) cycloalkylene-C(O)OH, -(C6-C 50 ) arylene-C(O)OH, -C(O)-NH-(C1-C 30 ) alkylene-(C6-C 50 ) arylene-(C1-C 30 ) alkylene-C(O)OH, -(C5-C 50 ) heteroarylene- C(O)OH, -C(O)-NH-(C1-C30 ) alkylene - OH, -C(O)-NH-(C3 - C 50 ) cycloalkylene - OH, -C(O)-NH-(C6 - C 50 ) arylene - OH, -C(O)-NH-(C5 - C 50 ) heteroarylene - OH, -C(O)-NH-(C1 - C 30 ) alkylene - C(O)OH, -C(O)-NH-(C3 - C 50 ) cycloalkylene - C(O)OH, -C(O)-NH-(C6 - C 50 ) arylene - C(O)OH, -C(O)-NH-(C5 - C 50 ) heteroarylene - C(O)OH, -(C1 - C 30 ) alkylene - C(O)-NH-(C1 - C 30 ) alkylene - C(O)OH, -(C1 - C 30 ) alkylene - C(O)-NH-(C3 - C 50 ) cycloalkylene - C(O)OH, -(C1 - C 30 ) alkylene - C(O)-NH-(C6 - C 50 ) arylene - C(O)OH, -(C1 - C 30 ) alkylene - C(O)-NH-(C5 - C 50 ) heteroarylene - C(O)OH, -(C1 - C 30 ) alkylene - P(O)2 - OH, -(C3 - C 50 ) cycloalkylene - P(O)2 - OH, -(C6 - C 50 ) arylene - P(O)2 - OH, -(C5 - C 50 ) heteroarylene - P(O)2 - OH, -C(O)-NH-(C1 - C 30 ) alkylene - O - P(-N(C1 - C 16 alkyl)2)-O-(C1 - C 30 ) alkylene - CN, -C(O)-NH-(C1 - C 30 ) alkylene - O - P(-N(C1 - C 16 alkyl)2)-O-(C1 - C 30 ) alkylene - OH, -C(O)-NH-(C1 - C 30 ) alkylene - O - P(-N(C1 - C 16 alkyl)2)-O-(C1 - C30 ) alkylene-C(O)OH, -C(O)-NH-(C1-C 30 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-NH2, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-CN, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-OH, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-C(O)OH, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-NH2, -(C1-C 30 ) alkylene -P(O)-OH, -(C3-C 50 ) cycloalkylene-P(O)-OH, -(C6-C 50 ) arylene-P(O)-OH, -(C5-C 50 ) -heteroarylene-P(O)-OH, -(C1-C 30 ) alkylene-P(O)(S)-OH,-(C3-C 50 ) cycloalkylene-P(O)(S)-OH,-(C6-C 50 ) arylene-P(O)(S)-OH,-(C5-C 50 ) heteroarylene-P(O)(S)-OH,-(C1-C 30 ) alkylene-CN, -(C3-C 50 ) cycloalkylene-CN, -(C6-C 50)Arylene-CN, -(C5-C 50 )Heteroarylene-CN, lipid, PEG, steroid, lipophilic substance, carbohydrate, cholesterol, adamantane, amino acid, peptide, chloroquine, alkaloid, and a substituent represented by formula BIII.

[0096]

Chemical formula

[0097] In some embodiments, R 7 ’ is selected from the group consisting of: -O-, -C(O)O-, -O-C(O)-, -P(O)2-O-, -O-P(O)2-O-, -P(O)(S)-O-, -O-P(O)(S)-O-, -O-P(O)-O-, -(C1-C 30 )alkylene-, -(C1-C 30 )alkylene-O-, -O-(C1-C 30 )alkylene-, -(C1-C 30 )alkylene-NH-, -NH-(C1-C 30 )alkylene-, -C(O)-(C1-C 30 )alkylene-, -(C1-C 30 )alkylene-C(O)-, -C(O)-O-(C1-C 30 )alkylene-, -(C1-C 30 )alkylene-C(O)-O-, -C(O)-NH-(C1-C 30 )alkylene-, -C(O)-NH-(C1-C 30 )alkylene-C(O)-O-, -C(O)-NH-(C1-C 30 )alkylene-O-C(O)-, -C(O)-NH-(C1-C 30 )alkylene-O-C(O)-O-, -C(O)-NH-(C1-C30 ) alkylene-O-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-O-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-C(O)-N((C1-C 20 ) alkyl)-, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-, -NH-C(O)-(C1-C 30 ) alkylene-, -NH-C(O)-(C1-C 30 ) alkylene-C(O)-O-, -NH-C(O)-(C1-C 30 ) alkylene-C(O)-, -NH-C(O)-(C1-C 30 ) alkylene-O-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-O-, -NH-C(O)-(C1-C30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-N((C1-C 20 ) alkyl)-C(O)-, -(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-, -(C1-C 30 ) alkylene -P(O)2-O-, -(C1-C 30 ) alkylene-O-P(O)2-O-, -(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-O-, -O-(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-NH-, -NH-(C3-C 50 ) cycloalkylene-, -C(O)-(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-C(O)-, -C(O)-O-(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-C(O)-O-, -C(O)-NH-(C3-C 50 ) cycloalkylene-, -C(O)-NH-(C3-C 50 ) cycloalkylene-C(O)-O-, -C(O)-NH-(C3-C 50 ) cycloalkylene-O-, -C(O)-N((C1-C20 )(alkyl)-(C3-C 50 )(cycloalkylene)-, -C(O)-N((C1-C 20 )(alkyl)-(C3-C 50 )(cycloalkylene)-O-, -C(O)-NH-(C3-C 50 )(cycloalkylene)-C(O)-NH-(C3-C 50 )(cycloalkylene)-, -C(O)-NH-(C3-C 50 )(cycloalkylene)-C(O)-NH-, -C(O)-N((C1-C 20 )(alkyl)-(C3-C 50 )(cycloalkylene)-C(O)-N((C1-C 20 )(alkyl)-(C3-C 50 )(cycloalkylene)-, -C(O)-N((C1-C 20 )(alkyl)-(C3-C 50 )(cycloalkylene)-C(O)-N((C1-C 20 )(alkyl)-, -(C3-C 50 )(cycloalkylene)-C(O)-NH-(C3-C 50 )(cycloalkylene)-C(O)-NH-(C3-C 50 )(cycloalkylene)-, -(C3-C 50 )(cycloalkylene)-C(O)-NH-(C3-C 50 )(cycloalkylene)-C(O)-NH-, -(C3-C 50 )(cycloalkylene) -P(O)2-O-, -(C3-C 50 )(cycloalkylene)-O-P(O)2-O-, -(C6-C 50 )(arylene)-, -(C6-C 50 )(arylene)-O-, -O-(C6-C 50 )(arylene)-, -(C6-C 50 )(arylene)-NH-, -NH-(C6-C 50 )(arylene)-, -C(O)-(C6-C 50 )(arylene)-, -(C6-C 50 )(arylene)-C(O)-, -C(O)-O-(C6-C 50 )(arylene)-, -(C6-C 50)arylene-C(O)-O-, -C(O)-NH-(C6-C 50 )arylene-, -C(O)-NH-(C6-C 50 )arylene-C(O)-O-, -C(O)-NH-(C6-C 50 )arylene-O-, -C(O)-N((C1-C 20 )alkyl)-(C6-C 50 )arylene-, -C(O)-N((C1-C 20 )alkyl)-(C6-C 50 )arylene-O-, -C(O)-NH-(C6-C 50 )arylene-C(O)-NH-(C3-C 50 )cycloalkylene-, -C(O)-NH-(C6-C 50 )arylene-C(O)-NH-, -C(O)-N((C1-C 20 )alkyl)-(C6-C 50 )arylene-C(O)-N((C1-C 20 )alkyl)-(C6-C 50 )arylene-, -C(O)-N((C1-C 20 )alkyl)-(C6-C 50 )arylene-C(O)-N((C1-C 20 )alkyl)-, -(C6-C 50 )arylene-C(O)-NH-(C6-C 50 )arylene-C(O)-NH-(C6-C 50 )arylene-, -(C6-C 50 )arylene-C(O)-NH-(C6-C 50 )arylene-C(O)-NH-, -(C6-C 50 )arylene -P(O)2-O-, -(C6-C 50 )arylene-O-P(O)2-O-, -(C5-C 50 )heteroarylene-, -(C5-C 50 )heteroarylene-O-, -O-(C5-C 50 )heteroarylene-, -(C5-C 50 )heteroarylene-NH-, -NH-(C5-C 50 )heteroarylene-, -C(O)-(C5-C 50 )heteroarylene-, -(C5-C50 ) heteroarylene-C(O)-, -C(O)-O-(C5-C 50 ) heteroarylene-, -(C5-C 50 ) heteroarylene-C(O)-O-, -C(O)-NH-(C5-C 50 ) heteroarylene-, -C(O)-NH-(C5-C 50 ) heteroarylene-C(O)-O-, -C(O)-NH-(C5-C 50 ) heteroarylene-O-, -C(O)-N((C1-C 20 ) alkyl)-(C5-C 50 ) heteroarylene-, -C(O)-N((C1-C 20 ) alkyl)-(C5-C 50 ) heteroarylene-O-, -C(O)-NH-(C5-C 50 ) heteroarylene-C(O)-NH-(C3-C 50 ) cycloalkylene-, -C(O)-NH-(C5-C 50 ) heteroarylene-C(O)-NH-, -C(O)-N((C1-C 20 ) alkyl)-(C5-C 50 ) heteroarylene-C(O)-N((C1-C 20 ) alkyl)-(C5-C 50 ) heteroarylene-, -C(O)-N((C1-C 20 ) alkyl)-(C5-C 50 ) heteroarylene-C(O)-N((C1-C 20 ) alkyl)-, -(C5-C 50 ) heteroarylene-C(O)-NH-(C5-C 50 ) heteroarylene-C(O)-NH-(C6-C 50 ) arylene-, -(C5-C 50 ) heteroarylene-C(O)-NH-(C5-C 50 ) heteroarylene-C(O)-NH-, -(C5-C 50 ) heteroarylene -P(O)2-O- and -(C5-C 50 ) heteroarylene-O-P(O)2-O-.

[0098] In some embodiments, R 8’ and R 9 ’ each is either non-existent or a substituent independently selected from the group consisting of: - hydrogen, hydroxyl, -(C1-C 30 )alkyl1, -(C3-C 50 )cycloalkyl, -(C6-C 50 )aryl, -(C1-C 30 )alkylene-OH, -(C3-C 50 )cycloalkylene-OH, -(C6-C 50 )arylene-OH, -(C1-C 30 )alkylene-C(O)OH, -(C3-C 50 )cycloalkylene-C(O)OH, -(C6-C 50 )arylene-C(O)OH, -(C1-C 30 )alkylene-NH2, -(C3-C 50 )cycloalkylene-NH2, -(C6-C 50 )arylene-NH2, -(C1-C 30 )alkoxy, -(C3-C 50 )cycloalkoxy, -(C6-C 50 )aryloxy, -C(O)-(C1-C 30 )alkyl, -OC(O)(C1-C 30 )alkyl, -C(O)-O-(C1-C 30 )alkyl, -C(O)-(C3-C 50 )cycloalkyl, -OC(O)-(C3-C 50 )cycloalkyl, -C(O)-O-(C3-C 50 )cycloalkyl, -C(O)- (C6-C 50 )aryloxy, -OC(O)-(C6-C 50 )aryloxy, -C(O)-O-(C6-C 50 )aryloxy, -C(O)-NH-(C1-C 30 )alkyl1, -C(O)-NH-(C3-C 50 )cycloalkyl, -C(O)-NH-(C6-C 50 )aryl, -(C1-C 30 )alkylene-phosphoric acid, -(C3-C 50)Cycloalkylene - phosphoric acid, -(C6 - C 50 )arylene - phosphoric acid. In some embodiments, R 8 ’ and each of R 9 ’ contains one or more hydroxyl groups, carboxyl groups, amino groups, and phosphate groups, which are optionally protected, for example, by a protecting group R P as defined herein. In one embodiment, R 8 ’ and R 9 ’ are bonded to each other, and R8’, R 9 ’, the carbon atom bonded to R8’, and the Y’ atom bonded to R9’ can form an unsubstituted or substituted heterocyclic ring. In another embodiment, when Y’ is oxygen, R 9 ’ does not exist.

[0099] In one embodiment, each R10’ is bonded to any one of P’, Q’, S’, T’ and is independently selected from the group consisting of hydroxyl, C(O)OH, -P(O)2 - OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C1 - C 30 )alkylene - OH, -(C3 - C 50 )cycloalkylene - OH, -(C6 - C 50 )arylene - OH, -(C5 - C 50 )heteroarylene - OH, -(C1 - C 30 )alkylene - C(O)OH, -(C3 - C 50 )cycloalkylene - C(O)OH, -(C6 - C 50 )arylene - C(O)OH, -(C5 - C 50 )heteroarylene - C(O)OH, -C(O)-NH-(C1 - C 30 )alkylene - OH, -C(O)-NH-(C3 - C 50 )cycloalkylene - OH, -C(O)-NH-(C6 - C 50 )arylene - OH, -C(O)-NH-(C5 - C 50 )heteroarylene - OH, -C(O)-NH-(C1 - C 30 )alkylene - C(O)OH, -C(O)-NH-(C3 - C 50)Cycloalkylene-C(O)OH, -C(O)-NH-(C6-C 50 )Arylene-C(O)OH, -C(O)-NH-(C5-C 50 )Heteroarylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C1-C 30 )Alkylene-C(O)OH, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-C(O)NH2, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-C(O)OH, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene- NH2, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-OH, -(C1-C 30 )Alkylene-C(O)-NH-(C3-C 50 )Cycloalkylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C6-C 50 )Arylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C5-C 50 )Heteroarylene-C(O)OH, -(C1-C 30 )Alkylene-P(O)2-OH, -(C3-C 50 )Cycloalkylene-P(O)2-OH, -(C6-C 50 )Arylene-P(O)2-OH, -(C5-C 50 )Heteroarylene-P(O)2-OH, -C(O)-NH-(C1-C 30 )Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 )Alkylene-CN, -C(O)-NH-(C1-C 30 )Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 )Alkylene-OH, -C(O)-NH-(C1-C 30) Alkylene - O - P(-N(C1 - C 16 ) Alkyl)2)-O-(C1 - C 30 ) Alkylene - C(O)OH, -C(O)-NH-(C1 - C 30 ) Alkylene - O - P(-N(C1 - C 16 ) Alkyl)2)-O-(C1 - C 30 ) Alkylene - NH2, -(C1 - C 30 ) Alkylene - C(O)-NH-(C1 - C 30 ) Alkylene - O - P(-N(C1 - C 16 ) Alkyl)2)-O-(C1 - C 30 ) Alkylene - CN, -(C1 - C 30 ) Alkylene - C(O)-NH-(C1 - C 30 ) Alkylene - O - P(-N(C1 - C 16 ) Alkyl)2)-O-(C1 - C 30 ) Alkylene - OH, -(C1 - C 30 ) Alkylene - C(O)-NH-(C1 - C 30 ) Alkylene - O - P(-N(C1 - C 16 ) Alkyl)2)-O-(C1 - C 30 ) Alkylene - C(O)OH, -(C1 - C 30 ) Alkylene - C(O)-NH-(C1 - C 30 ) Alkylene - O - P(-N(C1 - C 16 ) Alkyl)2)-O-(C1 - C 30 ) Alkylene - NH2, -(C1 - C 30 ) Alkylene - P(O)-OH, -(C3 - C 50 ) Cycloalkylene - P(O)-OH, -(C6 - C 50 ) Arylene - P(O)-OH, -(C5 - C 50 ) - Heteroarylene - P(O)-OH, -(C1 - C 30 ) Alkylene - P(O)(S)-OH,-(C3 - C 50 ) Cycloalkylene - P(O)(S)-OH,-(C6 - C 50 ) Arylene - P(O)(S)-OH,-(C5 - C 50 ) Heteroarylene - P(O)(S)-OH,-(C1 - C 30 ) Alkylene - CN, -(C3 - C50 ) Cycloalkylene-CN, -(C6-C 50 ) Arylene-CN, -(C5-C 50 ) Heteroarylene-CN, where one or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in R 10 ’ are optionally protected by R p as defined herein or are attached to a support material.

[0100] In one embodiment, B’, R 7 ’, R 8 ’, R 9 ’, and R 10 ’ contained in -(C1-C 30 ) alkylene- can include -(C1-C 28 ) alkylene-, or -(C1-C 26 ) alkylene-, or -(C1-C 24 ) alkylene-, or -(C2-C 22 ) alkylene-, or -(C3-C 20 ) alkylene-, or -(C4-C 18 ) alkylene-, or -(C5-C 17 ) alkylene-, or -(C6-C 16 ) alkylene-, or -(C7-C 14 ) alkylene-, or -(C8-C 12 ) alkylene-. In another embodiment, B’, R 7 ’, R 8 ’, R 9 ’, and R 10 ’ contained in -(C3-C 50 ) cycloalkylene- can include -(C3-C 40 ) cycloalkylene-, or -(C3-C 30 ) cycloalkylene-, or -(C3-C 22 ) cycloalkylene-, or -(C4-C 20 ) cycloalkylene-, or -(C5-C 18 ) cycloalkylene-, or -(C6-C 16 ) cycloalkylene-, or -(C7-C 14) cycloalkylene-, or -(C8-C 12 ) may include cycloalkylene-. In another embodiment, B’, R 7 ’, R 8 ’, R 9 ’, and R 10 ’ included in -(C6-C 50 ) arylene- may be -(C6-C 40 ) arylene-, or -(C6-C 30 ) arylene-, or -(C6-C 22 ) arylene-, or -(C6-C 20 ) arylene-, or -(C6-C 18 ) arylene-, or -(C6-C 16 ) arylene-, or -(C6-C 12 ) arylene-. In another embodiment, B’, R 7 ’, R 8 ’, R 9 ’, and R 10 ’ included in -(C5-C 50 [[ID=�6]]) heteroarylene- may be -(C5-C 40 ) heteroarylene-, or -(C5-C 30 ) heteroarylene-, or -(C5-C 22 ) heteroarylene-, or -(C5-C 18 ) heteroarylene-, or -(C6-C 16 ) heteroarylene-. In another embodiment, in each of substituents R 8 ’ and R 9 ’, the term “-(C1-C 30 ) alkyl” may include -(C2-C 22 ) alkyl, or -(C3-C 18 ) alkyl, or -(C4-C 16 ) alkyl, or -(C6-C 12 ) alkyl, or -(C8-C 10 ) alkyl; the term “-(C3-C 50 ) cycloalkyl” may be -(C4-C 40 ) cycloalkyl, or -(C5-C 30 ) cycloalkyl, or -(C6-C 20)Cycloalkyl, or -(C6-C 16 ) may contain cycloalkyl; the term "-(C6-C 50 ) aryl" means -(C6-C 40 ) aryl, or -(C6-C 30 ) aryl, or -(C6-C 25 ) aryl, or -(C6-C 22 ) aryl, or -(C6-C 16 ) aryl, or -(C6-C 12 ) aryl, or -(C6-C 50 ) aryloxy" means -(C6-C 40 ) aryloxy, or -(C6-C 30 ) aryloxy, or -(C6-C 25 ) aryloxy, or -(C6-C 22 ) aryloxy, or -(C6-C 16 ) aryloxy, or -(C6-C 12 ) may contain aryloxy.

[0101] In another embodiment, each R 11 ’ is attached to any one of P’, Q’, S’ and T’, does not exist, or is selected from the group consisting of. Hydrogen; hydroxyl; halogen atoms such as fluorine, chlorine, bromine, iodine; -(C1-C 20 ) alkyl, for example -(C2-C 19 ) alkyl, or -(C3-C 18 ) alkyl, or -(C4-C 16 ) alkyl, or -(C6-C 12 ) alkyl, or -(C8-C 10 ) alkyl; -(C1-C 20 ) alkoxy, for example -(C2-C 19 ) alkoxy, or -(C3-C 18 ) alkoxy, or -(C4-C 16 ) alkoxy, or -(C6-C 12 ) alkoxy; (C1-C 20Alkoxycarbonyl, for example (C1-C 16 ) alkoxycarbonyl, or (C2-C 12 ) alkoxycarbonyl, or (C3-C8) alkoxycarbonyl, or (C4-C6) alkoxycarbonyl; halogenated (C1-C 20 ) alkyl, for example halogenated (C2-C 19 ) alkyl, or halogenated (C3-C 18 ) alkyl, or halogenated (C4-C 16 ) alkyl, or halogenated (C6-C 12 ) alkyl, or halogenated (C8-C 10 ) alkyl; halogenated (C1-C 20 ) alkoxy, for example halogenated (C2-C 19 ) alkoxy, or halogenated (C3-C 18 ) alkoxy, or halogenated (C4-C 16 ) alkoxy, or halogenated (C6-C 12 ) alkoxy, or halogenated (C8-C 10 ) alkoxy; and halogenated (C1-C 20 ) alkoxycarbonyl, for example halogenated (C2-C 19 ) alkoxycarbonyl, or halogenated (C3-C 18 ) alkoxycarbonyl, or halogenated (C4-C 16 ) alkoxycarbonyl, or halogenated (C6-C 12 ) alkoxycarbonyl, or halogenated (C8-C 10 ) alkoxycarbonyl; where "halogenated" can be fluorination, chlorination, bromination, iodination, or a combination thereof.

[0102] In another embodiment, when Y' is oxygen, R 9 ' does not exist. In an exemplary embodiment, Y' is carbon and both R 8 ' and R 9 ' are present. In another embodiment, Y' is nitrogen, R8' is present, and R 9' does not exist. In another embodiment, Y' is nitrogen with a positive charge (i.e., quaternary ammonium), and R 8 ' and R 9 ' both exist. In another embodiment, Y' is sulfur or oxygen, and R 9 ' does not exist. In another embodiment, Y' is sulfur with a positive charge (i.e., sulfonium), and R 9 ' exists.

[0103] In one embodiment, m' is an integer of 1, 2, or 3, n' is an integer of 1, 2, or 3, and m' + n' = 4. In some exemplary embodiments, M' = 1 and N' = 3, or M' = 2 and N' = 2, or M' = 3 and N' = 1.

[0104] In one embodiment, each R 10 ' is bonded to any one of P', Q', S', T', and R11' is bonded to the remaining part of P', Q', S', T'. In one embodiment, R 10 ' is bonded to S', and the three R 11 ' are individually bonded to P', Q', T' respectively. In another embodiment, R 10 ' is bonded to Q', and the three R 11 ' are individually bonded to P', S', T' respectively. In another embodiment, R 10 ' is bonded to P', and the three R 11 ' are individually bonded to Q', S', T' respectively. In another embodiment, R 10 ' is bonded to T', and the three R 11 ' are individually bonded to P', Q', S' respectively. In another embodiment, two R 10 ' are bonded to Q' and S' respectively, and the two R 11 ' are bonded to P' and T' respectively.

[0105] In a specific embodiment, one or more hydroxyl groups, carboxyl groups, amino groups, phosphate groups contained in each of R 8 ', R 9 ', R 10 ' are terminal protecting groups R selected from the group consisting of the following pis optionally protected. (C1-C 22 ) alkyl, (C1-C 22 ) alkoxy, (C1-C 22 ) alkylcarbonyl, (C1-C 22 ) alkoxycarbonyl, (C6-C 22 ) aryl, (C6-C 22 ) aryloxy, (C6-C 22 ) arylcarbonyl, (C6-C 22 ) aryloxycarbonyl, tri((C1-C 22 ) alkyl)silyl and tri((C1-C 22 ) alkoxy)silyl, wherein the (C1-C p ) alkyl contained in the protecting group R 22 ) alkyl may be an alkyl containing from 1 to 22 carbon atoms, such as an alkyl containing from 2 to 20 carbon atoms, or from 3 to 18 carbon atoms, or from 4 to 16 carbon atoms, or from 6 to 12 carbon atoms. The (C1-C22) alkoxy contained in Rp may be an alkoxy containing from 1 to 22 carbon atoms, such as an alkoxy containing from 2 to 20 carbon atoms, or from 3 to 18 carbon atoms, or from 4 to 16 carbon atoms, or from 6 to 12 carbon atoms. The (C6-C22) aryl contained in Rp may be an aryl containing from 6 to 22 carbon atoms, such as an aryl containing from 6 to 20 carbon atoms, or from 6 to 18 carbon atoms, or from 6 to 16 carbon atoms, or from 6 to 12 carbon atoms, or from 8 to 10 carbon atoms. Also, the (C6-C22) aryloxy contained in Rp may be an aryloxy containing from 6 to 22 carbon atoms, and may be, for example, an aryloxy containing from 6 to 20 carbon atoms, from 6 to 18 carbon atoms, from 6 to 16 carbon atoms, from 6 to 12 carbon atoms, or from 8 to 10 carbon atoms.

[0106] In an exemplary embodiment, R 10The support material coupled to the ' may be selected from the group consisting of silica, silica gel, glass, ceramic, polymer, cellulose, and combinations thereof. In some embodiments, the solid material is in the form of beads. These beads can be made of any material such as magnetic beads, paramagnetic beads, silica beads, agarose beads, etc.

[0107] In another embodiment, the compound of the present disclosure may have a structure represented by any of Formula BIV to Formula BXIV.

[0108]

Chemical formula

[0109]

Chemical formula

[0110] Here, A1’, A2’, A3’, B’, C’, F’, G’, H’, I’, R 7 ’, R 8 ’, R 10 ’, R 11 ’, P’, Q’, S’, T’, m’, n’, M’ and N’ are as defined herein.

[0111] In one embodiment, Ring I can be formed by connecting A1’ and A2’, and thus can be composed of the nitrogen atom to which A1’ is attached, the carbon atom to which A2’ is attached, at least a part of A1’, and at least a part of A2’. Ring I may be a 4-, 5-, 6-, 7-, 8- or 9-membered ring, especially a ring fused to the core structure. For example, Ring I may be composed of a nitrogen atom, a carbon atom of the core structure, and 2, 3, 4, 5, 6, or 7 additional ring atoms derived from A1’ and A2’, and each of the additional ring atoms may be selected from the group consisting of carbon, nitrogen, oxygen, sulfur, and combinations thereof. In another exemplary embodiment, all of the additional ring atoms may be carbon atoms.

[0112] A4’ is a substituent bonded to any atom of Ring I, and A4’, A5’, and A6’ are each independently selected from the group consisting of: -R 1 ’, -O-R 1 ’, -S-R 1 ’, -C(O)-R 1 ’, -C(O)O-R 1 ’, -O-C(O)-R 1 ’, -C(O)NH-R 1 ’, -C(O)NR 2 ’-R 1 ’, -NH-C(O)-R 1 ’, -NR 2 ’-C(O)-R 1 ’, -O-P(O)2-O-R 1 ’, -OP(O)(S)-O-R 1 ’, -O-P(O)-O-R 1 ’, -NH-R 1 ’, -NR 2 ’-R 1 ’, -(CH2) r’ -NH-R 1 ’, -(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -R 1 ’, -C(O)-(CH2) r’ -NH-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -C(O)-R 1 ’, -C(O)-(CH2) r’ -C(O)O-R 1 ’, -C(O)-(CH2) r’ -NH-C(O)-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-C(O)-R 1 ’, -(CH2) r’ -C(O)-R 1 ’; -(CH2) r’ -C(O)O-R 1 ’; -(CH2)r’ -O-C(O)-R 1 ’, -(CH2) r’ -R 1 ’, -(CH2) r’ -NH-C(O)-R 1 ’, -(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’, -(CH2) r’ -NR 2 ’-C(O)-(CH2) s’ -R 1 ’, -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -N(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-NR 6’-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’); wherein, R 1 , R 2 ’, R 3 ’, R 4 ’, R 5 ’, R 6 ’, r’, s’, p’ and q’ are as defined herein.

[0113] In one embodiment, Ring II can be formed by connecting R 8 ’ and R 9 ’, and thus, it can be composed of the nitrogen atom to which R 9 ’ is attached, the carbon atom to which R 8 ’ is attached, at least a part of R 8 ’, and at least a part of R 9 ’. Ring II may be a 4-, 5-, 6-, 7-, 8- or 9-membered ring, or a ring fused to the core structure of substituent B’. For example, Ring II may be composed of a nitrogen atom, a carbon atom of the core structure of substituent B’, and R 8 ’ and R9 It may be composed of 2, 3, 4, 5, 6, or 7 additional ring atoms derived from '

[0114] In one embodiment, R 12 ’ is bonded to any atom of Ring II and is selected from the group consisting of: - hydrogen, hydroxyl, -(C1-C 30 )alkyl, -(C3-C 50 )cycloalkyl, -(C6-C 50 )aryl, -(C1-C 30 )alkylene-OH, -(C3-C 50 )cycloalkylene-OH, -(C6-C 50 )arylene-OH, -(C1-C 30 )alkylene-C(O)OH, -(C3-C 50 )cycloalkylene-C(O)OH, -(C6-C 50 )arylene-C(O)OH, -(C1-C 30 )alkylene-NH2, -(C3-C 50 )cycloalkylene-NH2, -(C6-C 50 )arylene-NH2, -(C1-C 30 )alkoxy, -(C3-C 50 )cycloalkoxy, -(C6-C 50 )aryloxy, -C(O)-(C1-C 30 )alkyl, -OC(O)(C1-C 30 )alkyl, -C(O)-O-(C1-C 30 )alkyl, -C(O)-(C3-C 50 )cycloalkyl, -OC(O)-(C3-C 50 )cycloalkyl, -C(O)-O-(C3-C 50 )cycloalkyl, -C(O)- (C6-C 50 )aryloxy, -OC(O)-(C6-C 50 )aryloxy, -C(O)-O-(C6-C 50)Aryloxy, -C(O)-NH-(C1-C 30 )Alkyl, -C(O)-NH-(C3-C 50 )Cycloalkyl, -C(O)-NH-(C6-C 50 )Aryl, -(C1-C 30 )Alkylene-phosphoric acid, -(C3-C 50 )Cycloalkylene-phosphoric acid, -(C6-C 50 )Arylene-phosphoric acid; wherein each -(C1-C 12 ’ contained in R 30 )alkyl may include -(C2-C 22 )alkyl, -(C3-C 18 )alkyl, -(C4-C 16 )alkyl, -(C6-C 12 )alkyl, -(C8-C10)alkyl. Here, each -(C3-C 50 )cycloalkyl contained in R12’ may include -(C4-C 40 )cycloalkyl, -(C5-C 30 )cycloalkyl, -(C6-C 20 )cycloalkyl, -(C6-C 16 )cycloalkyl. Each -(C6-C 12’ contained in R 50 )aryl may include -(C6-C 40 )aryl, -(C6-C 30 )aryl, -(C6-C 25 )aryl, -(C6-C 22 )aryl, -(C6-C 16 )aryl, -(C6-C 12 )aryl. Each -(C1-C 30 )alkoxy contained in R12’ may include -(C2-C 22 )alkoxy, -(C3-C 20 )alkoxy, -(C4-C 16 )alkoxy, -(C6-C 12 )alkoxy. Each -(C3-C 12’ contained in R 50 )cycloalkoxy may include -(C4-C 40 )cycloalkoxy, -(C5-C 30 )cycloalkoxy, -(C6-C20 ) cycloalkoxy, -(C6-C 16 ) may include cycloalkoxy. Each -(C6-C 50 ) aryloxy included in R12’ is -(C6-C 40 ) aryloxy, -(C6-C 30 ) aryloxy, -(C6-C 25 ) aryloxy, -(C6-C 22 ) aryloxy, -(C6-C 16 ) aryloxy, -(C6-C 12 ) may include aryloxy. Each -(C1-C 12’ ) alkylene- included in R 30 ) is -(C1-C 28 ) alkylene-, -(C1-C 26 ) alkylene-, -(C1-C 24 ) alkylene-, -(C2-C 22 ) alkylene-, -(C3-C 20 ) alkylene-, -(C4-C 18 ) alkylene-, -(C5-C 17 ) alkylene-, -(C6-C 16 ) alkylene-, -(C7-C 14 ) alkylene-, -(C8-C 12 ) may include alkylene-. The -(C3-C 50 ) cycloalkylene- included in R12’ is -(C3-C 40 ) cycloalkylene-, -(C3-C 30 ) cycloalkylene-, -(C3-C 22 ) cycloalkylene-, -(C4-C 20 ) cycloalkylene-, -(C5-C 18 ) cycloalkylene-, -(C6-C 16 ) cycloalkylene-, -(C7-C 14 ) cycloalkylene-, -(C8-C 12 ) may include cycloalkylene-; The -(C6-C50) arylene- included in R12’ is -(C6-C40) arylene-, -(C6-C 30 ) arylene-, -(C6-C 22 ) arylene-, -(C6-C 20 ) arylene-, -(C6-C18 ) arylene, -(C6-C 16 ) arylene, -(C6-C 12 ) may contain arylene-.

[0115] In some embodiments, one or more hydroxyl groups, carboxyl groups, and amino groups contained in R12’ may optionally be protected with a terminal protecting group RP selected from, for example, the group consisting of the following. (C1-C 22 ) alkyl, (C1-C 22 ) alkoxy, (C1-C 22 ) alkylcarbonyl, (C1-C 22 ) alkoxycarbonyl, (C6-C 22 ) aryl, (C6-C 22 ) aryloxy, (C6-C 22 ) arylcarbonyl, (C6-C 22 ) aryloxycarbonyl, tri((C1-C 22 ) alkyl)silyl and tri((C1-C 22 ) alkoxy)silyl, where the (C1-C 22 ) alkyl contained in the protecting group Rp is an alkyl containing 1 to 22 carbon atoms, for example an alkyl containing 2 to 20 carbon atoms, or 3 to 18 carbon atoms, or 4 to 16 carbon atoms, or 6 to 12 carbon atoms. The (C1-C 22 ) alkoxy contained in Rp is an alkoxy containing 1 to 22 carbon atoms, for example an alkoxy containing 2 to 20 carbon atoms, or 3 to 18 carbon atoms, or 4 to 16 carbon atoms, or 6 to 12 carbon atoms. The (C6-C 22 ) aryl contained in Rp is an aryl containing 6 to 22 carbon atoms, for example an aryl containing 6 to 20 carbon atoms, or 6 to 18 carbon atoms, or 6 to 16 carbon atoms, or 6 to 12 carbon atoms, or 8 to 10 carbon atoms. Also, the (C6-C 22) The aryloxy may be an aryloxy containing 6 to 22 carbon atoms, for example, an aryloxy containing 6 to 20 carbon atoms, 6 to 18 carbon atoms, 6 to 16 carbon atoms, 6 to 12 carbon atoms, or 8 to 10 carbon atoms. In a specific embodiment, the protecting group R P may be selected from the group consisting of benzyloxycarbonyl (Cbz), tert-butyldimethylsilyl (TBS), 4,4'-dimethoxytrityl (DMTr), tert-butyloxycarbonyl (Boc), benzyl (Bn), and benzyloxy (BnO).

[0116] In one embodiment, the compound of formula BI or formula BII can have one or more chiral centers, and each chiral center can independently be R chiral, S chiral, mesomeric, or racemic. For example, one or more of A1', A2', and A3' are selected from the following group: -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ')(-NH-C(O)-(CH2) q’ -R 3 '), -CH(-(CH2) r’ -C(O)-NH-(CH2) s’ -R 1 ')(-C(O)-NH-(CH2) q’ -R 3 '), -N(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ')(-NH-C(O)-(CH2) q’ -R 3 '), -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ')(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 '), -CR 4 '(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ')(-NH-C(O)-(CH2)q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), and the central carbon atom contained therein may be a chiral center.

[0117] In some embodiments, the compounds of the present disclosure have a structure represented by any one of Formula BXV to Formula BXX.

[0118] [Chemical formula]

[0119]

Chem.

[0120] Here, each of A1’, A2’, B’, R 7 ’, R 8 ’, and R 10 ’ is as defined herein.

[0121] In another embodiment, when one or more of the substituents shown above contain at least one double bond, each of the double bond and the atoms or sub-groups bonded thereto can be of the E or Z configuration.

[0122] In an exemplary embodiment, the compounds of the present disclosure have a structure represented by any of the following molecular formulas.

[0123]

Chem.

[0124]

Chem.

[0125]

Chem.

[0126]

Chem.

[0127]

Chem.

[0128]

Chem.

[0129]

Chem.

[0130]

Chem.

[0131]

Chem.

[0132]

Chem.

[0133]

Chem.

[0134]

Chem.

[0135]

Chem.

[0136]

Chem.

[0137]

Chem.

[0138]

Chem.

[0139]

Chem.

[0140]

Chem.

[0141]

Chem.

[0142]

Chem.

[0143]

Chem.

[0144]

Chem.

[0145]

Chem.

[0146]

Chem.

[0147]

Chem.

[0148]

Chem.

[0149]

Chem.

[0150]

Chem.

[0151]

Chem.

[0152] Here,

Chem.

[0153] In another embodiment of the present disclosure, an oligonucleotide delivery agent is provided that includes a DEC compound disclosed in this application and at least one oligonucleotide. When DEC is directly bound to the oligonucleotide or indirectly bound via at least one linking moiety, it can be fully understood that one or more terminal atoms (e.g., hydrogen, halogen, nitrogen, oxygen, sulfur, phosphorus, etc.) or terminal groups (e.g., hydroxyl group, amino group, ester group, ether group, acyl group, etc.) of DEC are cleaved to provide an active site that can be bound to the linking moiety or the oligonucleotide.

[0154] In one embodiment, the linking moiety, if present, can be selected from the group consisting of: -O-, -S-, -C(O)-, -NH-, -N((C1-C 12 )alkyl)-, -N((C1-C 12 )alkyl)-C(O)-O-, -O-C(O)-,-C(O)-O-,-O-C(O)-O-,-C(O)-NH-,-OP(O)2O-,-P(O)(O - )O-,-OP(O)O-,-OP(O)(S)O-,-O-S(O)2-O-,-S(O)2-O-,-S(O)-O-,-(C1-C 22 )alkylene-,-(C1-C 22) alkylene-NH-, -NH-(C1-C 22 ) alkylene-, -(C1-C 22 ) alkylene-NH-C(O)-, -(C1-C 22 ) alkylene-C(O)-, -(C1-C 22 ) alkylene-C(O)-O-, -C(O)-(C1-C 22 ) alkylene-, -NH-C(O)-(C1-C 22 ) alkylene-, -C(O)-NH-(C1-C 22 ) alkylene-, -C(O)-(C1-C 22 ) alkylene-NH-, -NH-(C1-C 22 ) alkylene-C(O)-, -C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-(C1-C 22 ) alkylene-NH-, -C(O)-(C1-C 22 ) alkylene-C(O)O-, -O-C(O)-(C1-C 22 ) alkylene-C(O)-O-, -C(O)-O-(C1-C 22 ) alkylene-O-C(O)-, -C(O)-(C1-C 22 ) alkylene-NH-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-NH-, -C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-, -(C1-C 22 ) alkylene-OP(O)2O-, -(C1-C 22 ) alkylene-OP(O)(O - ) O-,-(C1-C 22 ) alkylene-OP(O)(O - ) O-(C1-C 22 ) alkylene-, -(C1-C 22 ) alkylene-OP(O)O-, -(C1-C 22 ) alkylene-OP(O)(S)O-,-(C1-C 22 ) alkylene-O-S(O)2-O-, -(C1-C 22) alkylene-S(O)2-O-, -(C1-C 22 ) alkylene-S(O)-O-, -O-P(O)2-O-(C1-C 22 ) alkylene-OP(O)2O-, -O-P(O)-O-(C1-C 22 ) alkylene-OP(O)O-, -OP(O)(S)O-(C1-C 22 ) alkylene-OP(O)(S)O-,-O-S(O)2-O-(C1-C 22 ) alkylene-O-S(O)2-O-, -S(O)2-O-(C1-C 22 ) alkylene-S(O)2-O- and -O-S(O)-(C1-C 22 ) alkylene-S(O)-O-; wherein, the -(C1-C 22 ) alkylene included in the linking moiety can be an alkylene group containing from 1 to 22 carbon atoms, for example, an alkylene group containing from 2 to 20 carbon atoms, from 3 to 18 carbon atoms, from 4 to 16 carbon atoms, from 5 to 12 carbon atoms, from 6 to 10 carbon atoms. In one embodiment, when the linking moiety is a direct bond, the delivery enhancing compound is directly bonded to the oligonucleotide.

[0155] In another embodiment of the present disclosure, a delivery enhancing compound (DEC) conjugate oligonucleotide comprising a structure represented by formula AA is provided, which can deliver the oligonucleotide more efficiently both in vitro and in vivo.

[0156]

Chemical formula

[0157] In one embodiment of the present disclosure, the delivery enhancing compound (DEC) conjugate oligonucleotide has a structure represented by Formula BB.

[0158]

Chemical formula

[0159] Here, each of A1’, A2’, A3’, X’, F’, G’, H’, I’, C’, m’ and n’ is as defined above. In one embodiment, at least one of A1’, A2’ and A3’ contains one or more targeting moieties, and the DEC is bound to at least one oligonucleotide via the B” group. As described above, the B” group can be derived by detaching one or more terminal atoms (such as hydrogen, halogen, nitrogen, oxygen, sulfur, phosphorus, etc.) or one or more terminal groups (such as hydroxyl group, amino group, ester group, ether group, acyl group, etc.) from the B” group included in Formula BII.

[0160] In another embodiment of the present disclosure, the delivery enhancing compound (DEC) conjugate oligonucleotide has a structure represented by Formula BC.

[0161]

Chemical formula

[0162] Here, A1’, A2’, A3’, R7 ', R 9 ', R 10 ', R 11 Each of A1', X', Y', F', G', H', I', C', R', Q', S', T', m', n', M' and N' is as defined above. In one embodiment, at least one of A1', A2' and A3' comprises one or more targeting moieties, and DEC is R 8 is attached to at least one oligonucleotide via a " group. As described above, R 8 The " group is an R 8 "It can be derived by removing one or more terminal atoms (hydrogen, halogen, nitrogen, oxygen, sulfur, phosphorus, etc.) or one or more terminal groups (hydroxyl, amino, ester, ether, acyl, etc.) from the group.

[0163] In some embodiments of the present disclosure, the delivery-enhancing compound (DEC)-conjugated oligonucleotide has a structure represented by any one of formulas E1 to E15:

[0164] [ka]

[0165] [ka]

[0166] Here, A1', A2'R 7 ' and R 10 and each of A' and A' is as defined above. In one embodiment, at least one of A' and A' comprises one or more targeting moieties, or A' comprises one or more targeting moieties, and DEC is a B" group or R 8 is attached to at least one oligonucleotide via a " group. As described above, R 8 "The group is R 8"It can be derived by detaching one or more terminal atoms (such as hydrogen, halogen, nitrogen, oxygen, sulfur, phosphorus, etc.) or one or more terminal groups (such as hydroxyl group, amino group, ester group, ether group, acyl group, etc.) from the group. The "Group B" can be derived by detaching one or more terminal atoms (such as hydrogen, halogen, nitrogen, oxygen, sulfur, phosphorus, etc.) or one or more terminal groups (such as hydroxyl group, amino group, ester group, ether group, acyl group, etc.) from the "Group B".

[0167] In one embodiment, the targeting moiety is included in the molecular structure of the DEC compound as part of A1', A2' or A3', preferably as the group of R 1 ' or R 3 '. In another embodiment, the targeting moiety is independent of the DEC compound and is added after or during the synthesis of the DEC compound.

[0168] In one embodiment, the targeting moiety and the delivery enhancing compound moiety can be linked to each other by a first linking moiety. In one embodiment, the delivery enhancing compound moiety and the oligonucleotide can be linked by a second linking moiety. Each of the first and second linking moieties can be selected from the group consisting of direct bonds. -O-, -S-, -C(O)-, -NH-, -N((C1-C 12 )alkyl)-, -N((C1-C 12 )alkyl)-C(O)-O-, -O-C(O)-,-C(O)-O-, -O-C(O)-O-,-C(O)-NH-, -OP(O)2O-,-OP(O)O-, -OP(O)(S)O-, -O-S(O)2-O-,-S(O)2-O-, -S(O)-O-,-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-, -NH-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-C(O)-, -(C1-C 22 )alkylene-C(O)-, -(C1-C 22 )alkylene-C(O)-O-, -C(O)-(C1-C 22) alkylene-, -NH-C(O)-(C1-C 22 ) alkylene-, -C(O)-NH-(C1-C 22 ) alkylene-, -C(O)-(C1-C 22 ) alkylene-NH-, -NH-(C1-C 22 ) alkylene-C(O)-, -C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-(C1-C 22 ) alkylene-NH-, -C(O)-(C1-C 22 ) alkylene-C(O)O-, -O-C(O)-(C1-C 22 ) alkylene-C(O)-O-, -C(O)-O-(C1-C 22 ) alkylene-O-C(O)-, -C(O)-(C1-C 22 ) alkylene-NH-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-NH-, -NH-(C1-C 22 ) alkylene-OP(O)2O-, -NH-(C1-C 22 ) alkylene-CH((C1-C 22 ) alkylene-OH)-OP(O)2O-, -NH-(C1-C 22 ) alkylene-CH((C1-C 22 ) alkylene-OH)-(C1-C 22 ) alkylene-OP(O)2O-, -C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-, -(C1-C 22 ) alkylene-OP(O)2O-, -(C1-C 22 ) alkylene-OP(O)O-, -(C1-C 22 ) alkylene-OP(O)(S)O-,-(C1-C 22 ) alkylene-O-S(O)2-O-, -(C1-C 22 ) alkylene-S(O)2-O-, -(C1-C 22 ) alkylene-S(O)-O-, -O-P(O)2-O-(C1-C 22) alkylene-OP(O)2O-, -O-P(O)-O-(C1-C 22 ) alkylene-OP(O)O-, -OP(O)(S)O-(C1-C 22 ) alkylene-OP(O)(S)O-,-O-S(O)2-O-(C1-C 22 ) alkylene-O-S(O)2-O-, -S(O)2-O-(C1-C 22 ) alkylene-S(O)2-O- and -O-S(O)-(C1-C 22 ) alkylene-S(O)-O-; wherein, -(C1-C 22 ) alkylene- in the linking moiety is -(C1-C 20 ) alkylene-, or -(C1-C 18 ) alkylene-, or -(C1-C 16 ) alkylene-, or -(C2-C 12 ) alkylene-, or -(C3-C 10 ) alkylene-, or -(C4-C8) alkylene-, or -(C5-C6) alkylene- and can be. In one embodiment, in the delivery enhancing compound (DEC) conjugate oligonucleotide of formula A, when the linking moiety is a direct bond, the delivery enhancing compound moiety is directly bonded to the oligonucleotide. In one embodiment, in the delivery enhancing compound (DEC) conjugate oligonucleotide of formula BA, when the linking moiety is a direct bond, the targeting moiety is directly bonded to the delivery enhancing compound moiety.

[0169] The oligonucleotide may include those disclosed above, and in particular, may be selected from the group consisting of antisense oligonucleotides (ASO), antisense RNA, short interfering RNA (siRNA), microRNA (miRNA), saRNA, dsRNA, scRNA, sgRNA, or other oligonucleotides targeting at least one nucleic acid sequence.

[0170] All nucleotides of the oligonucleotides described herein may be natural nucleotides, i.e., unchemically modified nucleotides, or at least one nucleotide may be a chemically modified nucleotide. Non-limiting examples of chemical modifications include one or more of the following combinations.

[0171] 1) Modification of the phosphodiester bond of nucleotides in the oligonucleotide sequence; 2) Modification of the 2'-OH of ribose in the nucleotide; 3) Modification of the base in the nucleotide; 4) At least one nucleotide in the oligonucleotide sequence is a locked nucleic acid (LNA), and 5) At least one nucleotide in the oligonucleotide sequence is deoxyribonucleic acid (DNA).

[0172] Chemical modifications of the nucleotides or oligonucleotides in the present disclosure are well known to those skilled in the art. Modification of the phosphodiester bond refers to modification of oxygen in the phosphodiester bond, including phosphorothioate modification and boranophosphonate modification. The modifications disclosed herein stabilize the oligonucleotide structure and maintain high specificity and high affinity for base pairing. The modifications disclosed herein also stabilize the nucleic acid structure and maintain delivery-assisting properties including bioavailability, biodistribution, and / or cellular uptake of oligonucleotide agents in various tissues such as the prefrontal cortex, cerebellum, spinal cord (e.g., cervical, thoracic, lumbar), muscle, liver, and kidney.

[0173] In some embodiments, the chemical modification is to replace the phosphodiester bond on the backbone of the oligonucleotides disclosed herein with a phosphorothioate (PS) bond. In some embodiments, the oligonucleotides disclosed herein include at least one PS backbone modification in one of the oligonucleotide strands. In some embodiments, the oligonucleotide includes at least 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, or 40 PS backbone modifications in one oligonucleotide strand.

[0174] In some embodiments, the nucleotides or oligonucleotides in the present application include at least one chemically modified nucleotide modified at the 2'-OH of the pentose of the nucleotide, for example, 2'-fluoro modification, 2'-O-methyl modification, 2'-O-ethylidene methoxy modification, 2,4'-dinitrophenol modification, locked nucleic acid (LNA), 2'-amino modification or 2'-deoxy modification, for example, 2'-deoxy-2'-fluoro modified nucleotide, 2'-deoxy modified nucleotide.

[0175] In some embodiments, the nucleotides or oligonucleotides in the present application include at least one chemically modified nucleotide modified at the base of the nucleotide, for example, 5'-bromouracil modification, 5'-iodouracil modification, N-methyluracil modification, or 2,6-diaminopurine modification.

[0176] In some embodiments, the chemical modification of the nucleotide or oligonucleotide in the present application is the addition of an (E)-vinylphosphonate moiety at the 5'-end of the sense or antisense sequence. In some embodiments, the chemical modification of at least one chemically modified nucleotide is the addition of a 5'-methylcytosine moiety at the 5'-end of the sense sequence or antisense sequence. The oligonucleotides used in the present disclosure may be commercially available from various vendors or may be synthesized on a laboratory scale or an industrial scale. In an exemplary embodiment, the oligonucleotide can be synthesized by using conventional synthetic procedures, such as solid-phase synthesis techniques, using a commercially available synthesizer or a specially customized synthesizer such as a K&A DNA synthesizer purchased from K&A Laborgeraete GbR, Schaafheim, Germany, which involves sequentially adding batches of raw materials (e.g., phosphoramidite monomers including various linkers and conjugates) onto a solid support known in the art, and subjecting the addition of each base to a preparation cycle consisting of four chemical reactions: detritylation, coupling, oxidation / thiolation, and capping, to generate an oligonucleotide having the desired full length.

[0177] The oligonucleotide delivery agent may include one, two, three, four, five, six, or more oligonucleotides and one, two, three, four, five, six, or more delivery enhancing compounds separately linked via one, two, three, four, five, six, or more linking sites. For example, the oligonucleotide delivery agent may have a structure represented by any of the following formulas AAI to AAXXIV.

[0178]

Chemical formula

[0179]

Chemical formula

[0180] Here, L represents a linking moiety, [Chemical formula] represents an oligonucleotide delivery enhancing compound, and the symbol [Chemical formula] represents a double-stranded oligonucleotide having either symmetric or asymmetric ends at each terminus. [Chemical formula] represents a single-stranded oligonucleotide, and each of a, b, and c is independently an integer from 1 to 50, such as an integer from 2 to 45, or an integer from 3 to 40, or an integer from 4 to 35, or an integer from 5 to 30, or an integer from 10 to 20. Each of the linking moieties, and thus the delivery enhancing compound, can be linked at any internal position such as the 3'-terminus, 5'-terminus, or the nth nucleotide of the double-stranded or single-stranded oligonucleotide.

[0181] In one embodiment, one or more of the substituents A1, A2, A3, B, C, A1', A2', A3', B' and C' of the delivery enhancing compound can be linked to the linking moiety or the oligonucleotide (when the linking moiety is a direct bond). For example, one of A1, A2, A3, B, A1', A2', A3', R 8 ', R 12 ' and B', preferably A2, A2', B, B', R 8 ' or R 12 ' is linked to the linking moiety or the oligonucleotide. Without being limited to a particular theory, the above substituents (e.g., DMTrO-C1-C 22 alkylene- or -(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22)One or more terminal groups of (alkylene-CN) are cleaved or hydrolyzed to expose an active site (e.g., -(C1-C 22 ) alkylene-OH group), and can be bound to an oligonucleotide via a linking moiety (e.g., -P(O)(O-)O-). For example, exemplary structures of oligonucleotide delivery agents include O1 to O25 exemplified below.

[0182]

Chemical formula

[0183]

Chemical formula

[0184]

Chemical formula

[0185]

Chemical formula

[0186]

Chemical formula

[0187]

Chemical formula

[0188] Compound O6 (derived from Compound A10)

[0189]

Chemical formula

[0190]

Chem.

[0191]

Chem.

[0192]

Chem.

[0193]

Chem.

[0194]

Chem.

[0195]

Chem.

[0196]

Chem.

[0197]

Chem.

[0198]

Chem.

[0199]

Chem.

[0200]

Chem.

[0201]

Chem.

[0202]

Chem.

[0203]

Chem.

[0204]

Chem.

[0205]

Chem.

[0206]

Chem.

[0207]

Chem.

[0208] In all of Structures O1 - O25, the delivery enhancing compound is linked to the 3' or 5' end of the passenger (P) strand via a linking moiety, such as -OP(O)2O- (-P(O)(O-)-O-), where P is the passenger strand and G is the guide strand, to a double-stranded RNA (dsRNA) duplex (including but not limited to siRNA or saRNA) and / or a single-stranded antisense oligonucleotide (ASO). Also, electron rearrangement can occur.

[0209] In some embodiments, at least one hydrogen atom (i.e., H) contained in the delivery enhancing compound, delivery enhancing compound moiety, linking moiety, and / or oligonucleotide is replaced with a deuterium atom (i.e., D). In an exemplary embodiment, at least one of the delivery enhancing compound, delivery enhancing compound moiety, linking moiety, and oligonucleotide contains 1 - 20, such as 1 - 15, 1 - 12, 1 - 10, 1 - 8, 1 - 6, 1 - 3, 1 - 2 deuterium atoms. In an exemplary embodiment, 1% - 100%, or 2% - 90%, or 5% - 80%, or 10% - 70%, or 20% - 60%, or 30% - 50%, or 40% - 45% molar of the hydrogen atoms contained in the delivery enhancing compound, delivery enhancing compound moiety, linking moiety and / or oligonucleotide are replaced with deuterium atoms. In other exemplary embodiments, the deuterium substitution rate can be within a numerical range obtained by combining any two of the above-described endpoint values.

[0210] In another embodiment of the present disclosure, a pharmaceutical composition comprising an oligonucleotide delivery agent is provided. In one embodiment, the pharmaceutical composition can include one or more additional components such as pharmaceutically acceptable carriers, excipients, solvents, diluents, stabilizers, dispersants, buffers, solubilizers, preservatives, and combinations thereof.

[0211] In another embodiment of the present disclosure, there is provided a method for regulating the expression of a target gene in vitro or in vivo, including the step of administering a pharmaceutical composition to a subject or contacting the pharmaceutical composition with the cells of the subject. For example, the oligonucleotide delivery agent and the pharmaceutical composition can be applied to various organs, tissues, and cells such as the liver, lung, kidney, intestine, pancreas, gallbladder, heart, lymph node, spleen, stomach, bladder, muscle, bone, and central nervous system (CNS), and it is presumed that the expression of one or more target genes in these cells can be regulated.

[0212] Specific embodiments In a specific embodiment, the present disclosure provides an oligonucleotide delivery enhancing compound containing a nitrogen-containing 5-membered heterocyclic moiety. This compound contains at least one substituent that can be directly or indirectly bonded to the oligonucleotide.

[0213] In another specific embodiment, the oligonucleotide delivery enhancing compound has a structure represented by formula AI or formula AII.

[0214]

Chemical formula

Chemical formula

[0215] Here, m is an integer of 1, 2, or 3, n is an integer of 1, 2, or 3, and m + n = 4.

[0216] Here, C at each occurrence is hydrogen, a halogen atom, hydroxyl, (C1-C 20 ) alkyl, (C1-C 20) alkoxy, halogenated (C1-C 20 ) alkyl, and halogenated (C1-C 20 ) is selected from the group consisting of or not included in that group.

[0217] Here, B is independently selected from the group consisting of, in each occurrence. Hydroxyl, -C(O)OH, -P(O)2-OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C1-C 22 ) alkyl, -(C1-C 22 ) alkenyl, -(C1-C 22 ) alkylene-OH, -(C3-C 22 ) cycloalkylene-OH, -(C6-C 22 ) arylene-OH, -(C6-C 22 ) heteroarylene-OH, -(C1-C 22 ) alkylene-C(O)OH, -(C3-C 22 ) cycloalkylene-C(O)OH, -(C6-C 22 ) arylene-C(O)OH, -(C5-C 22 ) heteroarylene-C(O)OH, -O-C(O)-(C1-C 22 ) alkylene-C(O)NH2, -(C1-C 22 ) alkylene-O-C(O)-(C1-C 22 ) alkylene-C(O)NH2, -O-C(O)-(C1-C 22 ) alkylene-C(O)OH, -(C1-C 22 ) alkylene-O-C(O)-(C1-C 22 ) alkylene-C(O)OH, -C(O)-(C1-C 22 ) alkylene-C(O)NH2, -(C1-C 22 ) alkylene-C(O)-(C1-C 22 ) alkylene-C(O)NH2, -C(O)-NH-(C1-C 22 ) alkylene-OH, -C(O)-NH-(C1-C 22 ) alkylene-C(O)OH, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22) Alkylene-C(O)OH, -(C1-C 30 ) Alkylene-P(O)2-OH, -(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-CN, -(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-OH, -(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-NH2, -(C1-C<� 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-C(O)OH, -C(O)-NH-(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-CN, -C(O)-NH-(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-OH, -C(O)-NH-(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 30 ) Alkylene-C(O)OH, -C(O)-NH-(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-NH2, -(C1-C 22 ) Alkylene-C(O)-NH-(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-CN, -(C1-C 22 ) Alkylene-C(O)-NH-(C1-C 22 ) Alkylene-O-P(-N(C1-C It should be noted that there is a possible error in the original text where <� 22 seems to be an incorrect tag. It is recommended to double-check the original source for accuracy.22 (alkyl)2)-O-(C1-C 22 ) alkylene-OH, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 (alkyl)2)-O-(C1-C 22 ) alkylene-C(O)OH, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 (alkyl)2)-O-(C1-C 22 ) alkylene-NH2, -(C1-C 22 ) alkylene -P(O)-OH, -(C1-C 22 ) alkylene-P(O)(S)-OH,-(C1-C 22 ) alkylene-CN。

[0218] Here, each of A1, A2, and A3 is a substituent that is either absent or independently selected from the group consisting of: -H, -OH, -O-R 1 , -SH, -(C1-C 25 ) alkyl, halogenated -(C1-C 25 ) alkyl, -(C2-C 22 ) alkenyl, -(C1-C 22 ) alkylene-OH, -(C3-C 22 ) cycloalkyl, -(C3-C 22 ) cycloalkenyl, -(C1-C 22 ) alkylene-(C3-C 22 ) cycloalkyl, -(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-O-R 1 , -(C1-C 22 ) alkylene-COOR 1 , -C(O)O-R 1 ,-O-(C1-C 22 ) alkyl, -S-(C1-C 22 ) alkyl, -C(O)-R 1 , -C(O)-(C1-C22 ), alkyl, -O-C(O)-(C1-C 22 ), alkyl, -O-C(O)-R 1 , -(C1-C 22 ), alkylene-O-C(O)-R 1 , -C(O)-(C1-C 22 ), alkylene-OH, -C(O)-(C1-C 22 ), alkylene-R 1 , -C(O)-(C1-C 22 ), alkylene-NH-R 1 , -C(O)-(C1-C 22 ), alkylene-NR 2 -R 1 , -O-C(O)-(C1-C 22 ), alkylene-OH, -O-C(O)-(C1-C 22 ), alkylene-R 1 , -adamantyl, -(C1-C 22 ), alkylene-adamantyl, -O-adamantyl, -C(O)-(C1-C 22 ), alkylene-adamantyl, -(C1-C 22 ), alkylene-C(O)-(C1-C 22 ), alkylene-adamantyl, -NH-C(O)-(C1-C 22 ), alkylene-adamantyl, -(C1-C 22 ), alkylene-NH-C(O)-(C1-C 22 ), alkyl, -(C1-C 22 ), alkylene-NH-C(O)-halogenated (C1-C 22 ), alkyl, -CH(NH-CO-(C1-C 22 ), alkyl)-(C1-C 22 ), alkylene-NH-C(O)-(C1-C 22 ), alkyl, -C(O)-(C1-C 22 ), alkylene-C(O)-NH-C[-(C1-C 22 ), alkylene-O-(C1-C 22 ), alkylene-C(O)-NH-(C1-C 22 ), alkylene-NH-C(O)-(C1-C 22 ), alkyl]3, -C(O)-(C1-C22 ) alkylene-C(O)-NH-C[-(C1-C 22 ) alkylene-O-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-R 1 3, -CH(NH-CO-halogenated (C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-NH-C(O)-halogenated (C1-C 22 ) alkyl, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-NR 2 -C(O)-(C1-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-(C1-C6 alkylene oxide) (1-20) -NH-C(O)-(C1-C 22 ) alkylene-adamantyl, -C(O)NH-(C1-C 22 ) alkyl, -C(O)NH-R 1 , -C(O)NR 2 -R 1 , -C(O)NH-(C1-C 22 ) alkylene-OH, -C(O)NH-(C1-C 22 ) alkylene-COOH, -NH-C(O)-(C1-C 22 ) alkyl, -NH-C(O)-R 1 , -NR 2 -C(O)-R 1 , -O-P(O)2-O-R 1 ,-OP(O)(S)-O-R 1 ,-O-P(O)-O-R 1 , -NH-R 1 , -NR 2 -R 1 ,-(C1-C 22 ) alkylene-NH-R 1 , -(C1-C 22 ) alkylene-NR 2 -R1 , -C(O)-(C1-C 22 ) alkylene - C(O) - R 1 , -C(O)-(C1-C 22 ) alkylene - C(O)O - R 1 , -C(O)-(C1-C 22 ) alkylene - NH - C(O) - R 1 , -C(O)-(C1-C 22 ) alkylene - NR 2 - C(O) - R 1 , -(C1-C 22 ) alkylene - C(O) - R 1 , -(C1-C 22 ) alkylene - NH - C(O) - R 1 , -(C1-C 22 ) alkylene - NH - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - NH - C(O) - (C1-C 22 ) alkylene - NH - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - NH - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - NR 2 - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - CN, -(C1-C22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - OH, -(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - NH2, -(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - C(O)OH, -C(O)-NH-(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - CN, -C(O)-NH-(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - OH, -C(O)-NH-(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 30 ) alkylene - C(O)OH, -C(O)-NH-(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - NH2, -(C1 - C 22 ) alkylene - C(O)-NH-(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - CN, -(C1 - C 22 ) alkylene - C(O)-NH-(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C 22 ) alkylene - OH, -(C1 - C 22 ) alkylene - C(O)-NH-(C1 - C 22 ) alkylene - O - P(-N(C1 - C 22 alkyl)2)-O-(C1 - C22 ) alkylene-C(O)OH, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 ) alkylene-NH2, -(C1-C 22 ) alkylene -P(O)-OH, -(C1-C 22 ) alkylene-P(O)(S)-OH,-(C1-C 22 ) alkylene-CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzothiazole, and a substituent represented by formula AIII.

[0219]

Chemical formula

[0220] Here, each of R3, R4, and R5 is either absent or a substituent independently selected from the following group. -H, -OH, -O-R 1 , -SH, -(C1-C 25 ) alkyl, halogenated -(C1-C 25 ) alkyl, -(C2-C 22) alkenyl, -(C1-C 22 ) alkylene-OH, -(C3-C 22 ) cycloalkyl, -(C3-C 22 ) cycloalkenyl, -(C1-C 22 ) alkylene-(C3-C 22 ) cycloalkyl, -(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-O-R 1 , -(C1-C 22 ) alkylene-COOR 1 , -C(O)O-R 1 ,-O-(C1-C 22 ) alkyl, -S-(C1-C 22 ) alkyl, -C(O)-R 1 , -C(O)-(C1-C 22 ) alkyl, -O-C(O)-(C1-C 22 ) alkyl, -O-C(O)-R 1 , -(C1-C 22 ) alkylene-O-C(O)-R 1 , -C(O)-(C1-C 22 ) alkylene-OH, -C(O)-(C1-C 22 ) alkylene-R 1 , -C(O)-(C1-C 22 ) alkylene-NH-R 1 , -C(O)-(C1-C 22 ) alkylene-NR 2 -R 1 , -O-C(O)-(C1-C 22 ) alkylene-OH, -O-C(O)-(C1-C 22 ) alkylene-R 1 , -adamantyl, -(C1-C 22 ) alkylene-adamantyl, -O-adamantyl,-C(O)-(C1-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-C(O)-(C1-C 22 ) alkylene-adamantyl, -NH-C(O)-(C1-C 22) Alkylene - adamantyl, -(C1 - C 22 ) Alkylene - NH - C(O)-(C1 - C 22 ) Alkyl, -(C1 - C 22 ) Alkylene - NH - C(O)- halogenated (C1 - C 22 ) Alkyl, -CH(NH - CO-(C1 - C 22 ) Alkyl)-(C1 - C 22 ) Alkylene - NH - C(O)-(C1 - C 22 ) Alkyl, -C(O)-(C1 - C 22 ) Alkylene - C(O)-NH - C[-(C1 - C 22 ) Alkylene - O-(C1 - C 22 ) Alkylene - C(O)-NH-(C1 - C 22 ) Alkylene - NH - C(O)-(C1 - C 22 ) Alkyl]3, -C(O)-(C1 - C 22 ) Alkylene - C(O)-NH - C[-(C1 - C 22 ) Alkylene - O-(C1 - C 22 ) Alkylene - C(O)-NH-(C1 - C 22 ) Alkylene - NH - C(O)-(C1 - C 22 ) Alkylene - R 1 3, -CH(NH - CO - halogenated (C1 - C 22 ) Alkyl)-(C1 - C 22 ) Alkylene - NH - C(O)- halogenated (C1 - C 22 ) Alkyl, -(C1 - C 22 ) Alkylene - NH - C(O)-(C1 - C 22 ) Alkylene - adamantyl, -(C1 - C 22 ) Alkylene - NR 2 -C(O)-(C1 - C 22 ) Alkylene - adamantyl, -(C1 - C 22 ) Alkylene-(C1 - C6 alkylene oxide) (1-20) -NH - C(O)-(C1 - C 22 ) Alkylene - adamantyl, -C(O)NH-(C1 - C 22 ) Alkyl, -C(O)NH - R 1 , -C(O)NR 2 -R1 , -C(O)NH-(C1-C 22 ) alkylene-OH, -C(O)NH-(C1-C 22 ) alkylene-COOH, -NH-C(O)-(C1-C 22 ) alkyl, -NH-C(O)-R 1 , -NR 2 -C(O)-R 1 , -O-P(O)2-O-R 1 ,-OP(O)(S)-O-R 1 ,-O-P(O)-O-R 1 , -NH-R 1 , -NR 2 -R 1 ,-(C1-C 22 ) alkylene-NH-R 1 , -(C1-C 22 ) alkylene-NR 2 -R 1 , -C(O)-(C1-C 22 ) alkylene-C(O)-R 1 , -C(O)-(C1-C 22 ) alkylene-C(O)O-R 1 , -C(O)-(C1-C 22 ) alkylene-NH-C(O)-R 1 , -C(O)-(C1-C 22 ) alkylene-NR 2 -C(O)-R 1 , -(C1-C 22 ) alkylene-C(O)-R 1 , -(C1-C 22 ) alkylene-NH-C(O)-R 1 , -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-R 1, -(C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - C(O) - NH - (C1-C 22 ) alkylene - NH - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - NR 2 - C(O) - (C1-C 22 ) alkylene - R 1 , -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - CN, -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - OH, -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - NH2, -(C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - C(O)OH, -C(O) - NH - (C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - CN, -C(O) - NH - (C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 22 ) alkylene - OH, -C(O) - NH - (C1-C 22 ) alkylene - O - P(-N(C1-C 22 alkyl)2) - O - (C1-C 30 ) alkylene - C(O)OH, -C(O) - NH - (C1-C 22Alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )Alkylene-NH2, -(C1-C 22 )Alkylene-C(O)-NH-(C1-C 22 )Alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )Alkylene-CN, -(C1-C 22 )Alkylene-C(O)-NH-(C1-C 22 )Alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )Alkylene-OH, -(C1-C 22 )Alkylene-C(O)-NH-(C1-C 22 )Alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )Alkylene-C(O)OH, -(C1-C 22 )Alkylene-C(O)-NH-(C1-C 22 )Alkylene-O-P(-N(C1-C 22 alkyl)2)-O-(C1-C 22 )Alkylene-NH2, -(C1-C 22 )Alkylene -P(O)-OH, -(C1-C 22 )Alkylene-P(O)(S)-OH,-(C1-C 22 )Alkylene-CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, and substituted or unsubstituted benzothiazole.

[0221] Here, R 7 is, in each occurrence, bonded to any one of P, Q, S, and T and is selected from the group consisting of hydrogen, a halogen atom, a hydroxyl, (C1-C 20 )alkyl, (C1-C 20 )alkoxy, halogenated (C1-C 20 )alkyl, and halogenated (C1-C 20 )alkoxy, or is not included in that group.

[0222] Here, M is an integer of 0, 1, 2, or 3.

[0223] Here, R 6 is bonded to any one of P, Q, S, T and is selected from the group consisting of a direct bond, -O-, -C(O)O-, -O-C(O)-, -P(O)2-O-, -O-P(O)2-O-, -P(O)(S)-O-, -O-P(O)(S)-O-, -O-P(O)-O-, -(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-O-, -O-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-, -NH-(C1-C 22 )alkylene-, -C(O)-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-C(O)-, -C(O)-O-(C1-C 22 )alkylene-, -(C1-C 30 )alkylene-C(O)-O-, -C(O)-NH-(C1-C 22 )alkylene-, -C(O)-NH-(C1-C 22 )alkylene-C(O)-O-, -C(O)-NH-(C1-C 22 )alkylene-O-C(O)-, -C(O)-NH-(C1-C 22 )alkylene-O-C(O)-O-, -C(O)-NH-(C1-C 22 )alkylene-O-, -C(O)-N((C1-C 22 )alkyl)-(C1-C 22) alkylene-, -C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-O-, -C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-, -C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-, -C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-, -C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-, -C(O)-N((C1-C 22 ) alkyl)-(C1-C 22 ) alkylene-C(O)-N((C1-C 22 ) alkyl)-, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-, -(C1-C 22 ) alkylene-C(O)-NH-(C1-C 22 ) alkylene-C(O)-NH-, -NH-C(O)-(C1-C 22 ) alkylene-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-O-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-O-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-O-, -NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-, -NH-C(O)-(C1-C 22) alkylene-NH-C(O)-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-, -N((C1-C 22 ) alkyl)-C(O)-(C1-C 22 ) alkylene-N((C1-C 22 ) alkyl)-C(O)-, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22 ) alkylene-NH-C(O)-, -(C1-C 22 ) alkylene -P(O)2-O-, -(C1-C 22 ) alkylene-O-P(O)2-O-, -(C3-C 22 ) cycloalkylene-, -(C3-C 22 ) cycloalkylene-O-, -O-(C3-C 22 ) cycloalkylene-, -(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-O-, -O-(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-NH-, -NH-(C6-C 22 ) arylene-, -C(O)-(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-C(O)-, -C(O)-O-(C6-C 22 ) arylene-, -(C6-C 22 ) arylene-C(O)-O-, -C(O)-NH-(C6-C 22 ) arylene- and -C(O)-NH-(C6-C 22 ) arylene-C(O)-O-.

[0224] Here, R 1is, in each occurrence, independently selected from the group consisting of: hydrogen, hydroxyl, -(C1-C 22 )alkyl, -(C3-C 22 )cycloalkyl, -(C6-C 22 )aryl, -(C1-C 22 )alkoxy, -(C3-C 22 )cycloalkoxy, -(C6-C 22 )aryloxy, -C(O)-(C1-C 22 )alkyl, -OC(O)(C1-C 22 )alkyl, -C(O)-O-(C1-C 22 )alkyl, -C(O)-(C3-C 22 )cycloalkyl, -OC(O)-(C3-C 22 )cycloalkyl, -C(O)-O-(C3-C 22 )cycloalkyl, -C(O)-(C6-C 22 )aryloxy, -OC(O)-(C6-C 22 )aryloxy, -C(O)-O-(C6-C 22 )aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, glucosyl, acetamidoglucosyl, galactosamine, N-acetylgalactosamine, lipid, PEG, steroid, lipophilic, carbohydrate, cholesterol, adamantane, amino acid, peptide, chloroquine and alkaloid.

[0225] Here, R 2 is, in each occurrence, independently selected from the group consisting of a halogen atom, (C1-C 12 )alkyl, (C1-C 12 )alkoxy, (C1-C 12 )alkoxycarbonyl, (C6-C 16 )aryl, or (C6-C 16 )aryloxycarbonyl.

[0226] A1, A2, A3, B, C, R 1 , R 2 , R 3 , R 4, R 5 and R 6 One or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in R are optionally bonded to a support material or protected with a terminal protecting group.

[0227] However, provided that A1, A2, and A3 are not simultaneously hydrogen, and R 3 , R 4 and R 5 are not simultaneously hydrogen.

[0228] In another specific embodiment, there is provided an oligonucleotide delivery enhancing compound comprising a partial structure represented by formula BI and at least one substituent capable of being directly or indirectly bonded to the oligonucleotide.

[0229]

Chemical formula

[0230] Here, X’ is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur, each of F’, G’, H’, and I’ is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur, and each of the asterisks refers to a site optionally directly or indirectly bonded to at least one substituent or oligonucleotide.

[0231] In another specific embodiment, the oligonucleotide delivery enhancing compound has a structure represented by formula BII.

[0232]

Chemical formula

[0233] Here, X’ is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur, and each of F’, G’, H’, and I’ is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur.

[0234] Here, each of A1’, A2’ and A3’ is a substituent that either does not exist or is independently selected from the group consisting of: -H, -R 1 ’, -O-R 1 ’, -S-R 1 ’, -C(O)-R 1 ’, -C(O)O-R 1 ’, -O-C(O)-R 1 ’, -C(O)NH-R 1 ’, -C(O)NR 2 ’-R 1 ’, -NH-C(O)-R 1 ’, -NR 2 ’-C(O)-R 1 ’, -O-P(O)2-O-R 1 ’, -OP(O)(S)-O-R 1 ’, -O-P(O)-O-R 1 ’, -NH-R 1 ’, -NR 2 ’-R 1 ’, -(CH2) r’ -NH-R 1 ’, -(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -R 1 ’, -C(O)-(CH2) r’ -NH-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -C(O)-R 1 ’, -C(O)-(CH2) r’ -C(O)O-R 1 ’, -C(O)-(CH2) r’ -NH-C(O)-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-C(O)-R 1 ’, -(CH2) r’ -C(O)-R 1 ’; -(CH2) r’ -C(O)O-R 1 ’; -(CH2)r’ -O-C(O)-R 1 ’, -(CH2) r’ -R 1 ’, -(CH2) r’ -NH-C(O)-R 1 ’, -(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’, -(CH2) r’ -NH-C(O)-(C1-C 22 ) alkylene - NH - C(O) - (CH2) s’ -R 1 ’, -(CH2) r’ -C(O)-NH-(CH2) s’ -R 1 ’, -(CH2) r’ -C(O)- NH-(C1-C 22 ) alkylene - C(O) - NH - (CH2) s’ -R 1 ’, -(CH2) r’ -C(O)-NH-(C1-C 22 ) alkylene - NH - C(O) - (CH2) s’ -R 1 ’, -(CH2) r’ -NR 2 ’-C(O)-(CH2) s’ -R 1 ’, -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -C(O)-NH-(CH2) s’ -R 1 ’)(-C(O)-NH-(CH2) q’ -R 3 ’), -N(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NH-C(O)-(CH2)s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R3 ’), or A1’ and A2’ are combined to form an unsubstituted or substituted heterocyclic ring with the nitrogen atom bonded to A1’, the carbon atom bonded to A2’, A1’, and A2’. Here, each of R1’ and R3’ is independently selected from the group consisting of the following. Hydrogen, hydroxyl, -(C1-C 30 ) alkyl, -(C3-C 50 ) cycloalkyl, -(C6-C 50 ) aryl, -(C1-C 30 ) alkoxy, -(C3-C 50 ) cycloalkoxy, -(C6-C 50 ) aryloxy, -C(O)-(C1-C 30 ) alkyl, -OC(O)(C1-C 30 ) alkyl, -C(O)-O-(C1-C 30 ) alkyl, -C(O)-(C3-C 50 ) cycloalkyl, -OC(O)-(C3-C 50 ) cycloalkyl, -C(O)-O-(C3-C 50 ) cycloalkyl, -C(O)-(C6-C 50 ) aryloxy, -OC(O)-(C6-C 50 ) aryloxy, -C(O)-O-(C6-C 50 ) aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, glucosyl, acetamidoglucosyl, galactosamine, N-acetylgalactosamine, steroid, lipid, PEG, steroid, lipophilic, carbohydrate, cholesterol, adamantane, amino acid, peptide, ligand, nucleic acid, oligonucleotide, aptamer, small molecule, antibody, antibody fragment, chloroquine, alkaloid and target site, where one or more hydroxyl groups, carboxyl groups, R 1 ’ and the amino groups contained in each of R 3 ’ are optionally protected. Here, each of R 2 ’, R 4 ’, R 5 ’ and R 6 ’ is independently a halogen atom, (C1-C12 ) alkyl, (C1-C 12 ) alkoxy, (C1-C12) alkoxycarbonyl, (C6-C 16 ) aryl or (C6-C 16 ) aryloxycarbonyl.

[0235] Here, r’, s’, p’ and q’ are each an integer from 1 to 22, provided that when X’ is oxygen, A3’ does not exist, and A1’, A2’ and A3’ are not simultaneously hydrogen.

[0236] Here, each C’ is bonded to any one of F’, G’, H’, I’ and is selected from the group consisting of hydrogen, a halogen atom, hydroxyl, (C1-C 20 ) alkyl, (C1-C 20 ) alkoxy, halogenated (C1-C 20 ) alkyl, and halogenated (C1-C 20 ) alkoxy, or does not exist.

[0237] Here, m is an integer of 1, 2 or 3, n is an integer of 1, 2 or 3, and m + n = 4.

[0238] Here, each B’ is bonded to any one of F’, G’, H’, I’ and is independently selected from the following group. Hydroxyl, -C(O)OH, -(C1-C 30 ) alkoxy, -P(O)2-OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C1-C 30 ) alkylene-OH, -(C3-C 50 ) cycloalkylene-OH, -(C6-C 50 ) arylene-OH, -(C5-C 50 ) heteroarylene-OH, -(C1-C 30 ) alkylene-C(O)OH, -(C3-C 50 ) cycloalkylene-C(O)OH, -(C6-C 50 ) arylene-C(O)OH, -(C5-C 50) Heteroarylene-C(O)OH, -C(O)-NH-(C1-C 30 ) Alkylene-OH, -C(O)-NH-[(C1-C 30 ) Alkylene-O r’ -H (where r’ is an integer from 1 to 22), -C(O)-NH-[(C1-C 30 ) Alkylene-O r’ -(C1-C 30 ) Alkylene-C(O)OH (where r’ is an integer from 1 to 22), -C(O)-NH-(C3-C 50 ) Cycloalkylene-OH, -C(O)-NH-(C6-C 50 ) Arylene-OH, -C(O)-NH-(C5-C 50 ) Heteroarylene-OH, -C(O)-NH-(C1-C 30 ) Alkylene-C(O)OH, -C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)OH, -C(O)-NH-(C6-C 50 ) Arylene-C(O)OH, -C(O)-NH-(C1-C 30 ) Alkylene-(C6-C 50 ) Arylene-(C1-C 30 ) Alkylene-C(O)OH, -C(O)-NH-(C5-C 50 ) Heteroarylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C6-C 50 ) Arylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C5-C 50 ) Heteroarylene-C(O)OH, -(C1-C 30 ) Alkylene-P(O)2-OH, -(C3-C 50 ) Cycloalkylene-P(O)2-OH, -(C6-C 50) Allylene-P(O)2-OH, -(C5-C 50 ) Heteroarylene-P(O)2-OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-CN, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-C(O)OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-NH2, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-CN, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-NH2, -(C1-C 30 ) Alkylene -P(O)-OH, -(C3-C 50)Cycloalkylene-P(O)-OH, -(C6-C 50 )Arylene-P(O)-OH, -(C5-C 50 )-Heteroarylene-P(O)-OH, -(C1-C 30 )Alkylene-P(O)(S)-OH,-(C3-C 50 )Cycloalkylene-P(O)(S)-OH,-(C6-C 50 )Arylene-P(O)(S)-OH,-(C5-C 50 )Heteroarylene-P(O)(S)-OH,-(C1-C 30 )Alkylene-CN, -(C3-C 50 )Cycloalkylene-CN, -(C6-C 50 )Arylene-CN, -(C5-C 50 )Heteroarylene-CN, lipid, PEG, steroid, lipophilic substance, carbohydrate, cholesterol, adamantane, amino acid, peptide, chloroquine, alkaloid, and a substituent represented by formula BIII:

[0239]

Chemical formula

[0240] Here, Y’ is selected from the group consisting of carbon, nitrogen, oxygen and sulfur, each of P’, Q’, S’ and T’ is independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur, and the asterisk indicates the site where the substituent represented by formula BIII binds to any of F’, G’, H’ and I’ of formula BII.

[0241] Here, R 7 ' is selected from the group consisting of -O-, -C(O)O-, -O-C(O)-, -P(O)2-O-, -O-P(O)2-O-, -P(O)(S)-O-, -O-P(O)(S)-O-, -O-P(O)-O-, -(C1-C 30 )Alkylene-, -(C1-C 30 )Alkylene-O-, -O-(C1-C 30 )Alkylene-, -(C1-C 30 )Alkylene-NH-, -NH-(C1-C30 ) alkylene-, -C(O)-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-C(O)-, -C(O)-O-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-C(O)-O-, -C(O)-NH-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-O-, -C(O)-NH-(C1-C 30 ) alkylene-O-C(O)-, -C(O)-NH-(C1-C 30 ) alkylene-O-C(O)-O-, -C(O)-NH-(C1-C 30 ) alkylene-O-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-O-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-C(O)-N((C1-C 20 ) alkyl)-, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-, -(C1-C 30) alkylene-C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-, -NH-C(O)-(C1-C 30 ) alkylene-, -NH-C(O)-(C1-C 30 ) alkylene-C(O)-O-, -NH-C(O)-(C1-C 30 ) alkylene-C(O)-, -NH-C(O)-(C1-C 30 ) alkylene-O-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-O-, -NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-N((C1-C 20 ) alkyl)-C(O)-, -(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-, -(C1-C 30 ) alkylene -P(O)2-O-, -(C1-C 30 ) alkylene-O-P(O)2-O-, -(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-O-, -O-(C3-C 50 ) cycloalkylene-, -(C3-C50 ) Cycloalkylene-NH-, -NH-(C3-C 50 ) Cycloalkylene-, -C(O)-(C3-C 50 ) Cycloalkylene-, -(C3-C 50 ) Cycloalkylene-C(O)-, -C(O)-O-(C3-C 50 ) Cycloalkylene-, -(C3-C 50 ) Cycloalkylene-C(O)-O-, -C(O)-NH-(C3-C 50 ) Cycloalkylene-, -C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)-O-, -C(O)-NH-(C3-C 50 ) Cycloalkylene-O-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) Cycloalkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) Cycloalkylene-O-, -C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)-NH-(C3-C 50 ) Cycloalkylene-, -C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)-NH-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) Cycloalkylene-C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) Cycloalkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) Cycloalkylene-C(O)-N((C1-C 20 ) alkyl)-, -(C3-C 50 ) Cycloalkylene-C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)-NH-(C3-C 50 ) Cycloalkylene-, -(C3-C 50 ) Cycloalkylene-C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)-NH-, -(C3-C 50)Cycloalkylene-P(O)2-O-, -(C3-C 50 )Cycloalkylene-O-P(O)2-O-, -(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-O-, -O-(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-NH-, -NH-(C6-C 50 )Arylene-, -C(O)-(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-C(O)-, -C(O)-O-(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-C(O)-O-, -C(O)-NH-(C6-C 50 )Arylene-, -C(O)-NH-(C6-C 50 )Arylene-C(O)-O-, -C(O)-NH-(C6-C 50 )Arylene-O-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-O-, -C(O)-NH-(C6-C 50 )Arylene-C(O)-NH-(C3-C 50 )Cycloalkylene-, -C(O)-NH-(C6-C 50 )Arylene-C(O)-NH-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-C(O)-N((C1-C 20 )Alkyl)-, -(C6-C 50 )Arylene-C(O)-NH-(C6-C 50 )Arylene-C(O)-NH-(C6-C 50 )Arylene-, -(C6-C 50)arylene-C(O)-NH-(C6-C 50 )arylene-C(O)-NH-, -(C6-C 50 )arylene -P(O)2-O-, -(C6-C 50 )arylene-O-P(O)2-O-, -(C5-C 50 )heteroarylene-, -(C5-C 50 )heteroarylene-O-, -O-(C5-C 50 )heteroarylene-, -(C5-C 50 )heteroarylene-NH-, -NH-(C5-C 50 )heteroarylene-, -C(O)-(C5-C 50 )heteroarylene-, -(C5-C 50 )heteroarylene-C(O)-, -C(O)-O-(C5-C 50 )heteroarylene-, -(C5-C 50 )heteroarylene-C(O)-O-, -C(O)-NH-(C5-C 50 )heteroarylene-, -C(O)-NH-(C5-C 50 )heteroarylene-C(O)-O-, -C(O)-NH-(C5-C 50 )heteroarylene-O-, -C(O)-N((C1-C 20 )alkyl)-(C5-C 50 )heteroarylene-, -C(O)-N((C1-C 20 )alkyl)-(C5-C 50 )heteroarylene-O-, -C(O)-NH-(C5-C 50 )heteroarylene-C(O)-NH-(C3-C 50 )cycloalkylene-, -C(O)-NH-(C5-C 50 )heteroarylene-C(O)-NH-, -C(O)-N((C1-C 20 )alkyl)-(C5-C 50 )heteroarylene-C(O)-N((C1-C 20 )alkyl)-(C5-C 50 )heteroarylene-, -C(O)-N((C1-C 20 )alkyl)-(C5-C 50)Heteroarylene-C(O)-N((C1-C 20 )alkyl)-, -(C5-C 50 )heteroarylene-C(O)-NH-(C5-C 50 )heteroarylene-C(O)-NH-(C6-C 50 )arylene-, -(C5-C 50 )heteroarylene-C(O)-NH-(C5-C 50 )heteroarylene-C(O)-NH-, -(C5-C 50 )heteroarylene -P(O)2-O-, -(C5-C 50 )heteroarylene-O-P(O)2-O-.

[0242] Here, each of R8' and R9' is either absent or a substituent independently selected from the group consisting of -H, hydroxyl, -(C1-C 30 )alkyl, -(C3-C 50 )cycloalkyl, -(C6-C 50 )aryl, -(C1-C 30 )alkylene-OH, -(C3-C 50 )cycloalkylene-OH, -(C6-C 50 )arylene-OH, -(C1-C 30 )alkylene-C(O)OH, -(C3-C 50 )cycloalkylene-C(O)OH, -(C6-C 50 )arylene-C(O)OH, -(C1-C 30 )alkylene-NH2, -(C3-C 50 )cycloalkylene-NH2, -(C6-C 50 )arylene-NH2, -(C1-C 30 )alkoxy, -(C3-C 50 )cycloalkoxy, -(C6-C 50 )aryloxy, -C(O)-(C1-C 30 )alkyl, -OC(O)(C1-C 30 )alkyl, -C(O)-O-(C1-C 30 )alkyl, -C(O)-(C3-C 50 )cycloalkyl, -OC(O)-(C3-C50 ) cycloalkyl, -C(O)-O-(C3-C 50 ) cycloalkyl, -C(O)-(C6-C 50 ) aryloxy, -OC(O)-(C6-C 50 ) aryloxy, -C(O)-O-(C6-C 50 ) aryloxy, -C(O)-NH-(C1-C 30 ) alkyl, -C(O)-NH-(C3-C 50 ) cycloalkyl, -C(O)-NH-(C6-C 50 ) aryl, -(C1-C 30 ) alkylene-phosphate, -(C3-C 50 ) cycloalkylene-phosphate, -(C6-C 50 ) arylene-phosphate. Here, R 8 ’ and R 9 ’ Each of the one or more hydroxyl groups, carboxyl groups, amino groups, and phosphate groups contained in is optionally protected with a terminal protecting group. Or, R 8 ’ and R 9 ’ are bonded to each other, and R 8 ’, R 9 ’, the carbon atom bonded to R 8 ’, and the Y’ atom bonded to R 9 ’ form an unsubstituted or substituted heterocyclic ring. However, when Y’ is oxygen or sulfur, R 9 ’ does not exist.

[0243] Each R 10 ’ is bonded to any one of P’, Q’, S’, T’ and is independently selected from the group consisting of hydroxyl, C(O)OH, -P(O)2-OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C1-C 30 ) alkylene-OH, -(C3-C 50 ) cycloalkylene-OH, -(C6-C 50 ) arylene-OH, -(C5-C 50 ) heteroarylene-OH, -(C1-C 30 ) alkylene-C(O)OH, -(C3-C 50)Cycloalkylene-C(O)OH, -(C6-C 50 )Arylene-C(O)OH, -(C5-C 50 )Heteroarylene - C(O)OH, -C(O)-NH-(C1-C 30 )Alkylene-OH, -C(O)-NH-(C3-C 50 )Cycloalkylene-OH, -C(O)-NH-(C6-C 50 )Arylene-OH, -C(O)-NH-(C5-C 50 )Heteroarylene-OH, -C(O)-NH-(C1-C 30 )Alkylene-C(O)OH, -C(O)-NH-(C3-C 50 )Cycloalkylene-C(O)OH, -C(O)-NH-(C6-C 50 )Arylene-C(O)OH, -C(O)-NH-(C5-C 50 )Heteroarylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C1-C 30 )Alkylene-C(O)OH, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-C(O)NH2, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-C(O)OH, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene- NH2, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-OH, -(C1-C 30 )Alkylene-C(O)-NH-(C3-C 50 )Cycloalkylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C6-C 50 )Arylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C5-C 50 )Heteroarylene-C(O)OH, -(C1-C 30 )Alkylene-P(O)2-OH, -(C3-C50 ) Cycloalkylene-P(O)2-OH, -(C6-C 50 ) Arylene-P(O)2-OH, -(C5-C 50 ) Heteroarylene-P(O)2-OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-CN, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-C(O)OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-NH2, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-CN, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-NH2, -(C1-C30 ) alkylene -P(O)-OH, -(C3-C 50 ) cycloalkylene-P(O)-OH, -(C6-C 50 ) arylene-P(O)-OH, -(C5-C 50 ) -heteroarylene-P(O)-OH, -(C1-C 30 ) alkylene-P(O)(S)-OH,-(C3-C 50 ) cycloalkylene-P(O)(S)-OH,-(C6-C 50 ) arylene-P(O)(S)-OH,-(C5-C 50 ) heteroarylene-P(O)(S)-OH,-(C1-C 30 ) alkylene-CN, -(C3-C 50 ) cycloalkylene-CN, -(C6-C 50 ) arylene-CN, -(C5-C 50 ) heteroarylene-CN, where one or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in R 10 ’ are optionally protected with Rp or attached to a support material as defined herein.

[0244] Here, each R 11 is bonded to any of P’, Q’, S’, and T’ and is selected from the group consisting of hydrogen, a halogen atom, hydroxyl, (C1-C 20 ) alkyl, (C1-C 20 ) alkoxy, (C1-C 20 ) alkoxycarbonyl, halogenated (C1-C 20 ) alkyl, and halogenated (C1-C 20 ) alkoxycarbonyl, or is not included in that group.

[0245] Here, M’ is an integer of 1, 2, or 3, N’ is an integer of 1, 2, or 3, and M’ + N’ = 4.

[0246] In another specific embodiment, A1, A2, A3, B, C, R 1 , R 2 , R3 , R 4 , R 5 ,R 6 , R 1 ’, R 2 ’, R 3 ’, R 4 ’, R 5 ’, R 6 ’, R 7 ’, R 8 ’, R 9 ’, R 10 ’ and R 11 ’ Each of the one or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained therein is optionally protected by a terminal protecting group RP selected from the group consisting of the following. (C1-C 22 ) alkyl, (C1-C 22 ) alkoxy, (C1-C 22 ) alkylcarbonyl, (C1-C 22 ) alkoxycarbonyl, (C6-C 22 ) aryl, (C6-C 22 ) aryloxy, (C6-C 22 ) arylcarbonyl, (C6-C 22 ) allyloxycarbonyl, glucosyl, acetamidoglucosyl, galactosamine, N-acetylgalactosamine, tri((C1-C 22 ) alkyl)silyl, and tri((C1-C 22 ) alkoxy)silyl.

[0247] Here, the support material is selected from the group consisting of silica, silica gel, glass, ceramic, polymer, cellulose, and combinations thereof.

[0248] In another specific embodiment, the oligonucleotide delivery enhancing compound has a structure represented by any of Formula AIV to Formula AXIII and Formula BIV to BXIV.

[0249]

Chemical formula

[0250] [Chemical formula]

[0251] Here, A1, A2, A3, A4, F, G, H, I, B, C, P, Q, S, T, R6, R7, m, n, and M are as defined herein.

[0252] Here, each of Ring I and Ring II is a 4-, 5-, 6-, 7-, 8-, or 9-membered ring.

[0253] Here, A4’ is bonded to any atom of Ring I, and each of A4’, A5’, and A6’ is independently selected from the group consisting of: -R 1 ’, -O-R 1 ’, -S-R 1 ’, -C(O)-R 1 ’, -C(O)O-R 1 ’, -O-C(O)-R 1 ’, -C(O)NH-R 1 ’, -C(O)NR 2 ’-R 1 ’, -NH-C(O)-R 1 ’, -NR 2 ’-C(O)-R 1 ’, -O-P(O)2-O-R 1 ’, -OP(O)(S)-O-R 1 ’, -O-P(O)-O-R 1 ’, -NH-R 1 ’, -NR 2 ’-R 1 ’, -(CH2) r’ -NH-R 1 ’, -(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -R 1 ’, -C(O)-(CH2) r’ -NH-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2)r’ -C(O)-R 1 ’, -C(O)-(CH2) r’ -C(O)O-R 1 ’, -C(O)-(CH2) r’ -NH-C(O)-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-C(O)-R 1 ’, -(CH2) r’ -C(O)-R 1 ’; -(CH2) r’ -C(O)O-R 1 ’; -(CH2) r’ -O-C(O)-R 1 ’, -(CH2) r’ -R 1 ’, -(CH2) r’ -NH-C(O)-R 1 ’, -(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’, -(CH2) r’ -NR 2 ’-C(O)-(CH2) s’ -R 1 ’, -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -N(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’((CH2) r’ -NR 5 ’-C(O)-(CH2) s’ -R 1 ’)((CH2) p’ -NR 6 ’-C(O)-(CH2) q’ -R 3 ’).

[0254] Here, each of R1’ and R3’ is independently selected from the group consisting of: hydrogen, hydroxyl, -(C1-C 30 ) alkyl, -(C3-C 50 ) cycloalkyl, -(C6-C50 ) aryl, -(C1-C 30 ) alkoxy, -(C3-C 50 ) cycloalkoxy, -(C6-C 50 ) aryloxy, -C(O)-(C1-C 30 ) alkyl, -OC(O)(C1-C 30 ) alkyl, -C(O)-O-(C1-C 30 ) alkyl, -C(O)-(C3-C 50 ) cycloalkyl, -OC(O) -(C3-C 50 ) cycloalkyl, -C(O)-O-(C3-C 50 ) cycloalkyl, -C(O)- (C6-C 50 ) aryloxy, -OC(O)-(C6-C 50 ) aryloxy, -C(O)-O-(C6-C 50 ) aryloxy, -C(O)- phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, lipid, PEG, steroid, lipophilic substance, carbohydrate, cholesterol, adamantane, amino acid, peptide, ligand, nucleic acid, oligonucleotide, aptamer, small molecule, antibody, antibody fragment, polyethylene glycol, carbohydrate, antibody, antibody fragment, chloroquine, alkaloid and target molecule, R 1 ’ and R 3 ’ each of the one or more hydroxyl groups, carboxyl groups, amino groups contained therein is optionally protected. Here, R 2 ’, R 4 ’, R 5 ’ and R 6 ’ each is, independently of one another, a halogen atom, (C1-C 12 ) alkyl, (C1-C 12 ) alkoxy, (C6-C 16 ) aryl or (C6-C 16 ) aryloxy. Here, each of r’, s’, p’ and q’ is an integer from 1 to 22.

[0255] Here, R 12’ is bonded to any atom of Ring II and is selected from the group consisting of: - hydrogen, hydroxyl, -(C1-C 30 )alkyl, -(C3-C 50 )cycloalkyl, -(C6-C 50 )aryl, -(C1-C 30 )alkylene-OH, -(C3-C 50 )cycloalkylene-OH, -(C6-C 50 )arylene-OH, -(C1-C 30 )alkylene-C(O)OH, -(C3-C 50 )cycloalkylene-C(O)OH, -(C6-C 50 )arylene-C(O)OH, -(C1-C 30 )alkylene-NH2, -(C3-C 50 )cycloalkylene-NH2, -(C6-C 50 )arylene-NH2, -(C1-C 30 )alkoxy, -(C3-C 50 )cycloalkoxy, -(C6-C 50 )aryloxy, -C(O)-(C1-C 30 )alkyl, -OC(O)(C1-C 30 )alkyl, -C(O)-O-(C1-C 30 )alkyl, -C(O)-(C3-C 50 )cycloalkyl, -OC(O)-(C3-C 50 )cycloalkyl, -C(O)-O-(C3-C 50 )cycloalkyl, -C(O)- (C6-C 50 )aryloxy, -OC(O)-(C6-C 50 )aryloxy, -C(O)-O-(C6-C 50 )aryloxy, -C(O)-NH-(C1-C 30 )alkyl, -C(O)-NH-(C3-C 50 )cycloalkyl, -C(O)-NH-(C6-C 50 )aryl, -(C1-C 30 )alkylene-phosphate, -(C3-C 50 )cycloalkylene-phosphate, -(C6-C50 )Arylene-phosphoric acid. Here, R 12 One or more hydroxyl groups, carboxyl groups, amino groups, and phosphate groups contained in ’ are optionally protected.

[0256] In another specific embodiment, each of F, G, H, and I is carbon, m is 1 and n is 3, B is bonded to G or H, each of P, Q, S, and T is carbon, and R6 is bonded to either Q or S.

[0257] Here, the protecting group R P is selected from the group consisting of benzyloxycarbonyl (Cbz), tert-butyldimethylsilyl (TBS), 4,4’-dimethoxytrityl (DMTr), t-butyloxycarbonyl (Boc), benzyl (Bn), and benzyloxy (BnO). Here, C in each occurrence is selected from the group consisting of hydrogen, a halogen atom, hydroxyl, (C1-C 12 )alkyl, (C1-C 12 )alkoxy, halogenated (C1-C 12 )alkyl, and halogenated (C1-C 12 )alkoxy.

[0258] Here, B in each occurrence is selected from the group consisting of: -(C1-C 22 )alkylene-OH, -O-C(O)-(C1-C 16 )alkylene-C(O)NH2, -(C1-C 16 )alkylene-O-C(O)-(C1-C 16 )alkylene-C(O)NH2, -O-C(O)-(C1-C 16 )alkylene-C(O)OH, -(C1-C 16 )alkylene-O-C(O)-(C1-C 16 )alkylene-C(O)OH, -C(O)-(C1-C 16 )alkylene-C(O)NH2, -(C1-C 16 )alkylene-C(O)-(C1-C 16) alkylene-C(O)NH2, -C(O)-NH-(C1-C 16 ) alkylene-OH, -C(O)-NH-(C1-C 16 ) alkylene-C(O)OH, -(C1-C 16 ) alkylene-C(O)-NH-(C1-C 16 ) alkylene-C(O)OH, -(C1-C 16 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 16 ) alkylene-CN, -(C1-C 16 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 16 ) alkylene-OH, -(C1-C 16 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 16 ) alkylene-NH2, -(C1-C 16 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 16 ) alkylene-C(O)OH, and -C(O)-NH-(C1-C 16 ) alkylene-O-P(-N(C1-C 16 alkyl)2)-O-(C1-C 16 ) alkylene-CN.

[0259] Here, each of A1, A2, and A3 is a substituent that is either absent or independently selected from the group consisting of: -H, -OH, linear or branched -(C6-C 22 ) alkyl, linear or branched -(C2-C 22 ) alkenyl, -(C1-C 22 ) alkylene-OH, -(C3-C 22 ) cycloalkyl, -(C3-C 22 ) cycloalkenyl, -(C1-C 22 ) alkylene-(C3-C 22 ) cycloalkyl, -(C1-C 22 ) alkylene-R 1 , -(C1-C 22Alkylene-O-R 1 , -(C1-C 22 )Alkylene-COOR 1 , -O-(C1-C 22 )Alkyl, -(C6-C 22 )Alkylene-adamantyl, -(C1-C 22 )Alkylene-NH-C(O)-(C1-C 22 )Alkyl, -(C1-C 22 )Alkylene-NH-C(O)-(C1-C 22 )Alkylene-adamantyl, -(C1-C 22 )Alkylene-NR 2 -C(O)-(C1-C 22 )Alkylene-adamantyl, -(C1-C 22 )Alkylene-(C1-C6 alkylene oxide) (1-20) -NH-C(O)-(C1-C 22 )Alkylene-adamantyl, -C(O)NH-R 1 ,-(C1-C 22 )Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 )Alkylene-CN, -(C1-C 22 )Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 )Alkylene-OH, -(C1-C 22 )Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 )Alkylene-NH2, -(C1-C 22 )Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 )Alkylene-C(O)OH, -C(O)-NH-(C1-C 22 )Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22) Alkylene-CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzothiazole, and a substituent represented by formula AIII.

[0260] Here, Y is selected from the group consisting of carbon, nitrogen, oxygen and sulfur, and each of P, Q, S and T is carbon.

[0261] Here, R 3 , R 4 , R 5 Each of is either absent or a substituent independently selected from the group consisting of: -H, -OH, linear or branched -(C6-C 22 ) alkyl, linear or branched -(C2-C 22 ) alkenyl, -(C1-C 22 ) alkylene-OH, -(C3-C 22 ) cycloalkyl, -(C3-C 22 ) cycloalkenyl, -(C1-C 22 ) alkylene-(C3-C 22 ) cycloalkyl, -(C1-C 22 ) alkylene-R 1 , -(C1-C 22 ) alkylene-O-R 1 , -(C1-C 22 ) alkylene-COOR 1 , -O-(C1-C 22 ) alkyl, -(C6-C 22 ) alkylene-adamantyl, -(C1-C 22 ) alkylene-NH-C(O)-(C1-C 22) Alkyl, -(C1-C 22 ) Alkylene-NH-C(O)-(C1-C 22 ) Alkylene-adamantyl, -(C1-C 22 ) Alkylene-NR 2 -C(O)-(C1-C 22 ) Alkylene-adamantyl, -(C1-C 22 ) Alkylene-(C1-C6 alkylene oxide) (1-20) -NH-C(O)-(C1-C 22 ) Alkylene-adamantyl, -C(O)NH-R 1 ,-(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-CN, -(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-OH, -(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-NH2, -(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22 ) Alkylene-C(O)OH, -C(O)-NH-(C1-C 22 ) Alkylene-O-P(-N(C1-C 22 Alkyl)2)-O-(C1-C 22)Alkylene-CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzothiazole.

[0262] Here, R 7 is bonded to any one of P, Q, S, and T in each occurrence and is selected from or not included in the group consisting of hydrogen, a halogen atom, hydroxyl, (C1-C 20 )alkyl, (C1-C 20 )alkoxy, halogenated (C1-C 20 )alkyl, and halogenated (C1-C 20 )alkoxy.

[0263] Here, M is an integer of 0, 1, 2, or 3.

[0264] Here, R 6 is bonded to any one of P, Q, S, and T and is selected from the group consisting of: -(C1-C 16 )alkylene-, -(C1-C 16 )alkylene-O-, -O-(C1-C 16 )alkylene-, -(C1-C 16 )alkylene-NH-, -NH-(C1-C 16 )alkylene-, -C(O)-(C1-C 16 )alkylene-, -(C1-C 16 )alkylene-C(O)-, -C(O)-O-(C1-C 16 )alkylene-, -(C1-C16)alkylene-C(O)-O-, -C(O)-NH-(C1-C 16) alkylene-, -C(O)-NH-(C1-C 16 ) alkylene-C(O)-O-, -C(O)-NH-(C1-C 16 ) alkylene-O-C(O)-, -C(O)-NH-(C1-C 16 ) alkylene-O-C(O)-O-, -C(O)-NH-(C1-C 16 ) alkylene-O-, -C(O)-N((C1-C 16 ) alkyl)-(C1-C 16 ) alkylene-, -C(O)-N((C1-C 16 ) alkyl)-(C1-C 16 ) alkylene-O-, -C(O)-NH-(C1-C 16 ) alkylene-C(O)-NH-(C1-C 16 ) alkylene-, -C(O)-NH-(C1-C 16 ) alkylene-NH-C(O)-(C1-C 16 ) alkylene-, -C(O)-NH-(C1-C 16 ) alkylene-C(O)-NH-, -C(O)-N((C1-C 16 ) alkyl)-(C1-C 16 ) alkylene-C(O)-N((C1-C 16 ) alkyl)-(C1-C 16 ) alkylene-, -C(O)-N((C1-C 16 ) alkyl)-(C1-C 16 ) alkylene-C(O)-N((C1-C 16 ) alkyl)-, -(C1-C 16 ) alkylene-C(O)-NH-(C1-C 16 ) alkylene-C(O)-NH-(C1-C 16 ) alkylene-, -(C1-C 16 ) alkylene-C(O)-NH-(C1-C 16 ) alkylene-C(O)-NH-, -NH-C(O)-(C1-C 16 ) alkylene-, -NH-C(O)-(C1-C 16 ) alkylene-C(O)-O-, -NH-C(O)-(C1-C 16 ) alkylene-C(O)-, -NH-C(O)-(C1-C 16) alkylene-O-, -N((C1-C 16 ) alkyl)-C(O)-(C1-C 16 ) alkylene-, -N((C1-C 16 ) alkyl)-C(O)-(C1-C 16 ) alkylene-O-, -NH-C(O)-(C1-C 16 ) alkylene-NH-C(O)-(C1-C 16 ) alkylene-, -NH-C(O)-(C1-C 16 ) alkylene-NH-C(O)-, -N((C1-C 16 ) alkyl)-C(O)-(C1-C 16 ) alkylene-N((C1-C 16 ) alkyl)-C(O)-(C1-C 16 ) alkylene-, -N((C1-C 16 ) alkyl)-C(O)-(C1-C 16 ) alkylene-N((C1-C 16 ) alkyl)-C(O)-, -(C1-C 16 ) alkylene-NH-C(O)-(C1-C 16 ) alkylene-NH-C(O)-(C1-C 16 ) alkylene-, -(C1-C 16 ) alkylene-NH-C(O)-(C1-C 16 ) alkylene-NH-C(O)-.

[0265] In another specific embodiment, the oligonucleotide delivery enhancing compound has a structure represented by any one of Formula BXV to Formula BXXIX.

[0266]

Chemical formula

[0267] Here, each of A1' and A2' is a substituent independently selected from the group consisting of: -R 1 ', -O-R 1 ', -S-R 1 ', -C(O)-R 1 ', -C(O)O-R 1’, -O-C(O)-R 1 ’, -C(O)NH-R 1 ’, -C(O)NR 2 ’-R 1 ’, -NH-C(O)-R 1 ’, -NR 2 ’-C(O)-R 1 ’, -O-P(O)2-O-R 1 ’, -OP(O)(S)-O-R 1 ’, -O-P(O)-O-R 1 ’, -NH-R 1 ’, -NR 2 ’-R 1 ’, -(CH2) r’ -NH-R 1 ’, -(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -R 1 ’, -C(O)-(CH2) r’ -NH-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-R 1 ’, -C(O)-(CH2) r’ -C(O)-R 1 ’, -C(O)-(CH2) r’ -C(O)O-R 1 ’, -C(O)-(CH2) r’ -NH-C(O)-R 1 ’, -C(O)-(CH2) r’ -NR 2 ’-C(O)-R 1 ’, -(CH2) r’ -C(O)-R 1 ’; -(CH2) r’ -C(O)O-R 1 ’; -(CH2) r’ -O-C(O)-R 1 ’, -(CH2) r’ -R 1 ’, -(CH2) r’ -NH-C(O)-R 1 ’, -(CH2) r’ -NH-C(O)-(CH2)s’ -R 1 ’, -(CH2) r’ -NH-C(O)-(C1-C 22 ) alkylene - NH - C(O) - (CH2) s’ -R 1 ’, -(CH2) r’ -C(O)-NH-(CH2) s’ -R 1 ’, -(CH2) r’ -C(O)- NH-(C1-C 22 ) alkylene - C(O) - NH - (CH2) s’ -R 1 ’, -(CH2) r’ -C(O)-NH-(C1-C 22 ) alkylene - NH - C(O) - (CH2) s’ -R 1 ’, -(CH2) r’ -NR 2 ’-C(O)-(CH2) s’ -R 1 ’, -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -C(O)-NH-(CH2) s’ -R 1 ’)(-C(O)-NH-(CH2) q’ -R 3 ’), -N(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-NH-C(O)-(CH2) q’ -R 3 ’), -CH(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ’)(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 ’), -CR 4 ’(-(CH2) r’ -NH-C(O)-(CH2) s’-R 1 ')(-NH-C(O)-(CH2) q’ -R 3 '), -CR 4 '(-(CH2) r’ -NH-C(O)-(CH2) s’ -R 1 ')(-(CH2) p’ -NH-C(O)-(CH2) q’ -R 3 '), -CH(-(CH2) r’ -NR 5 '-C(O)-(CH2) s’ -R 1 ')(-NR 6 '-C(O)-(CH2) q’ -R 3 '), -CH(-(CH2) r’ -NR 5 '-C(O)-(CH2) s’ -R 1 ')(-(CH2) p’ -NR 6 '-C(O)-(CH2) q’ -R 3 '), -CR 4 '((CH2) r’ -NR 5 '-C(O)-(CH2) s’ -R 1 ')((CH2) p’ -NR 6 '-C(O)-(CH2) q’ -R 3 '), and -CR 4 '((CH2) r’ -NR 5 '-C(O)-(CH2) s’ -R 1 ')((CH2) p’ -NR 6 '-C(O)-(CH2) q’ -R 3 '). where R 1 ' and R 3 Each of C′ is independently selected from the group consisting of: 30 ) alkyl, -(C3-C 50 )cycloalkyl, -(C6-C 50)Aryl, -(C1-C 30 )Alkoxy, -(C3-C 50 )Cycloalkoxy, -(C6-C 50 )Aryloxy, -C(O)-(C1-C 30 )Alkyl, -OC(O)(C1-C 30 )Alkyl, -C(O)-O-(C1-C 30 )Alkyl, -C(O)-(C3-C 50 )Cycloalkyl, -OC(O)-(C3-C 50 )Cycloalkyl, -C(O)-O-(C3-C 50 )Cycloalkyl, -C(O)-(C6-C 50 )Aryloxy, -OC(O)-(C6-C 50 )Aryloxy, -C(O)-O-(C6-C 50 )Aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, lipid, PEG, steroid, lipophilic substance, carbohydrate, cholesterol, adamantane, amino acid, peptide, ligand, nucleic acid, oligonucleotide, aptamer, small molecule, antibody, antibody fragment, polyethylene glycol, antibody, antibody fragment, chloroquine, alkaloid and target molecule. Here, one or more hydroxyl groups, carboxyl groups, amino groups contained in each of R1’ and R3’ are optionally protected. Here, each of R2’, R4’, R5’ and R6’ is independently a halogen atom, (C1-C 12 )Alkyl, (C1-C 12 )Alkoxy, (C1-C 12 )Alkoxycarbonyl, (C6-C 16 )Aryl or (C6-C 16 )Aryloxycarbonyl. Here, each of r’, s’, p’ and q’ is an integer from 1 to 22.

[0268] Here, m is an integer of 1, 2 or 3, n is an integer of 1, 2 or 3, and m + n = 4.

[0269] Here, it is independently selected from the group consisting of each B'. Hydroxyl, -C(O)OH, -(C1-C 30 ) alkoxy, -P(O)2-OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C1-C 30 ) alkylene-OH, -(C3-C 50 ) cycloalkylene-OH, -(C6-C 50 ) arylene-OH, -(C5-C 50 ) heteroarylene-OH, -(C1-C 30 ) alkylene-C(O)OH, -(C3-C 50 ) cycloalkylene-C(O)OH, -(C6-C 50 ) arylene-C(O)OH, -(C5-C 50 ) heteroarylene-C(O)OH, -C(O)-NH-(C1-C 30 ) alkylene-OH, -C(O)-NH-[(C1-C 30 ) alkylene-O] r’ -H (where r' is an integer from 1 to 22), -C(O)-NH-[(C1-C 30 ) alkylene-O] r’ -(C1-C 30 ) alkylene-C(O)-OH (where r' is an integer from 1 to 22), -C(O)-NH-(C3-C 50 ) cycloalkylene-OH, -C(O)-NH-(C6-C 50 ) arylene-OH, -C(O)-NH-(C5-C 50 ) heteroarylene-OH, -C(O)-NH-(C1-C 30 ) alkylene-C(O)OH, -C(O)-NH-(C3-C 50 ) cycloalkylene-C(O)OH, -C(O)-NH-(C6-C 50 ) arylene-C(O)OH, -C(O)-NH-(C1-C 30 ) alkylene-(C6-C 50 ) arylene-(C1-C 30 ) alkylene-C(O)OH, -C(O)-NH-(C5-C 50 ) heteroarylene-C(O)OH, -(C1-C 30) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C3-C 50 ) Cycloalkylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C6-C 50 ) Arylene-C(O)OH, -(C1-C 30 ) Alkylene-C(O)-NH-(C5-C 50 ) Heteroarylene-C(O)OH, -(C1-C 30 ) Alkylene-P(O)2-OH, -(C3-C 50 ) Cycloalkylene-P(O)2-OH, -(C6-C 50 ) Arylene-P(O)2-OH, -(C5-C 50 ) Heteroarylene-P(O)2-OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-CN, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-C(O)OH, -C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-NH2, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30 ) Alkylene-CN, -(C1-C 30 ) Alkylene-C(O)-NH-(C1-C 30 ) Alkylene-O-P(-N(C1-C 16(Alkyl)2)-O-(C1-C 30 ) alkylene-OH, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-O-P(-N(C1-C 16 (Alkyl)2)-O-(C1-C 30 ) alkylene-C(O)OH, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-O-P(-N(C1-C 16 (Alkyl)2)-O-(C1-C 30 ) alkylene-NH2, -(C1-C 30 ) alkylene -P(O)-OH, -(C3-C 50 ) cycloalkylene-P(O)-OH, -(C6-C 50 ) arylene-P(O)-OH, -(C5-C 50 ) -heteroarylene-P(O)-OH, -(C1-C 30 ) alkylene-P(O)(S)-OH,-(C3-C 50 ) cycloalkylene-P(O)(S)-OH,-(C6-C 50 ) arylene-P(O)(S)-OH,-(C5-C 50 ) heteroarylene-P(O)(S)-OH,-(C1-C 30 ) alkylene-CN, -(C3-C 50 ) cycloalkylene-CN, -(C6-C 50 ) arylene-CN, -(C5-C 50 ) heteroarylene-CN, lipid, PEG, steroid, lipophilic substance, carbohydrate, cholesterol, adamantane, amino acid, peptide, chloroquine, alkaloid.

[0270] Here, each R7' is selected from the group consisting of: -O-, -C(O)O-, -O-C(O)-, -P(O)2-O-, -O-P(O)2-O-,-P(O)(S)-O-, -O-P(O)(S)-O-, -O-P(O)-O-, -(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-O-, -O-(C1-C 30) alkylene-, -(C1-C 30 ) alkylene-NH-, -NH-(C1-C 30 ) alkylene-, -C(O)-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-C(O)-, -C(O)-O-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-C(O)-O-, -C(O)-NH-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-O-, -C(O)-NH-(C1-C 30 ) alkylene-O-C(O)-, -C(O)-NH-(C1-C 30 ) alkylene-O-C(O)-O-, -C(O)-NH-(C1-C 30 ) alkylene-O-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-O-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C1-C 30 ) alkylene-C(O)-N((C1-C 20 ) alkyl)-, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-(C1-C30 ) alkylene-, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-C(O)-NH-, -NH-C(O)-(C1-C 30 ) alkylene-, -NH-C(O)-(C1-C 30 ) alkylene-C(O)-O-, -NH-C(O)-(C1-C 30 ) alkylene-C(O)-, -NH-C(O)-(C1-C 30 ) alkylene-O-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-O-, -NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-, -N((C1-C 20 ) alkyl)-C(O)-(C1-C 30 ) alkylene-N((C1-C 20 ) alkyl)-C(O)-, -(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-, -(C1-C 30 ) alkylene-NH-C(O)-(C1-C 30 ) alkylene-NH-C(O)-, -(C1-C 30 ) alkylene -P(O)2-O-, -(C1-C 30 ) alkylene-O-P(O)2-O-, -(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-O-, -O-(C3-C50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-NH-, -NH-(C3-C 50 ) cycloalkylene-, -C(O)-(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-C(O)-, -C(O)-O-(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-C(O)-O-, -C(O)-NH-(C3-C 50 ) cycloalkylene-, -C(O)-NH-(C3-C 50 ) cycloalkylene-C(O)-O-, -C(O)-NH-(C3-C 50 ) cycloalkylene-O-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) cycloalkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) cycloalkylene-O-, -C(O)-NH-(C3-C 50 ) cycloalkylene-C(O)-NH-(C3-C 50 ) cycloalkylene-, -C(O)-NH-(C3-C 50 ) cycloalkylene-C(O)-NH-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) cycloalkylene-C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) cycloalkylene-, -C(O)-N((C1-C 20 ) alkyl)-(C3-C 50 ) cycloalkylene-C(O)-N((C1-C 20 ) alkyl)-, -(C3-C 50 ) cycloalkylene-C(O)-NH-(C3-C 50 ) cycloalkylene-C(O)-NH-(C3-C 50 ) cycloalkylene-, -(C3-C 50 ) cycloalkylene-C(O)-NH-(C3-C 50)Cycloalkylene-C(O)-NH-, -(C3-C 50 )Cycloalkylene -P(O)2-O-, -(C3-C 50 )Cycloalkylene-O-P(O)2-O-, -(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-O-, -O-(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-NH-, -NH-(C6-C 50 )Arylene-, -C(O)-(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-C(O)-, -C(O)-O-(C6-C 50 )Arylene-, -(C6-C 50 )Arylene-C(O)-O-, -C(O)-NH-(C6-C 50 )Arylene-, -C(O)-NH-(C6-C 50 )Arylene-C(O)-O-, -C(O)-NH-(C6-C 50 )Arylene-O-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-O-, -C(O)-NH-(C6-C 50 )Arylene-C(O)-NH-(C3-C 50 )Cycloalkylene-, -C(O)-NH-(C6-C 50 )Arylene-C(O)-NH-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-, -C(O)-N((C1-C 20 )Alkyl)-(C6-C 50 )Arylene-C(O)-N((C1-C 20 )Alkyl)-, -(C6-C 50 )Arylene-C(O)-NH-(C6-C 50) Arylene-C(O)-NH-(C6-C 50 ) Arylene-, -(C6-C 50 ) Arylene-C(O)-NH-(C6-C 50 ) Arylene-C(O)-NH-, -(C6-C 50 ) Arylene -P(O)2-O-, -(C6-C 50 ) Arylene-O-P(O)2-O-, -(C5-C 50 ) Heteroarylene-, -(C5-C 50 ) Heteroarylene-O-, -O-(C5-C 50 ) Heteroarylene-, -(C5-C 50 ) Heteroarylene-NH-, -NH-(C5-C 50 ) Heteroarylene-, -C(O)-(C5-C 50 ) Heteroarylene-, -(C5-C 50 ) Heteroarylene-C(O)-, -C(O)-O-(C5-C 50 ) Heteroarylene-, -(C5-C 50 ) Heteroarylene-C(O)-O-, -C(O)-NH-(C5-C 50 ) Heteroarylene-, -C(O)-NH-(C5-C 50 ) Heteroarylene-C(O)-O-, -C(O)-NH-(C5-C 50 ) Heteroarylene-O-, -C(O)-N((C1-C 20 ) Alkyl)-(C5-C 50 ) Heteroarylene-, -C(O)-N((C1-C 20 ) Alkyl)-(C5-C 50 ) Heteroarylene-O-, -C(O)-NH-(C5-C 50 ) Heteroarylene-C(O)-NH-(C3-C 50 ) Cycloalkylene-, -C(O)-NH-(C5-C 50 ) Heteroarylene-C(O)-NH-, -C(O)-N((C1-C 20 ) Alkyl)-(C5-C 50 ) Heteroarylene-C(O)-N((C1-C 20 ) Alkyl)-(C5-C 50)Heteroarylene-, -C(O)-N((C1-C 20 )alkyl)-(C5-C 50 )heteroarylene-C(O)-N((C1-C 20 )alkyl)-, -(C5-C 50 )heteroarylene-C(O)-NH-(C5-C 50 )heteroarylene-C(O)-NH-(C6-C 50 )arylene-, -(C5-C 50 )heteroarylene-C(O)-NH-(C5-C 50 )heteroarylene-C(O)-NH-, -(C5-C 50 )heteroarylene -P(O)2-O-, -(C5-C 50 )heteroarylene-O-P(O)2-O-.

[0271] Here, each R8’ is a substituent independently selected from the group consisting of: -H, hydroxyl, -(C1-C 30 )alkyl, -(C3-C 50 )cycloalkyl, -(C6-C 50 )aryl, -(C1-C 30 )alkylene-OH, -(C3-C 50 )cycloalkylene-OH, -(C6-C 50 )arylene-OH, -(C1-C 30 )alkylene-C(O)OH, -(C3-C 50 )cycloalkylene-C(O)OH, -(C6-C 50 )arylene-C(O)OH, -(C1-C 30 )alkylene-NH2, -(C3-C 50 )cycloalkylene-NH2, -(C6-C 50 )arylene-NH2, -(C1-C 30 )alkoxy, -(C3-C 50 )cycloalkoxy, -(C6-C 50 )aryloxy, -C(O)-(C1-C 30 )alkyl, -OC(O)(C1-C 30 )alkyl, -C(O)-O-(C1-C 30) Alkyl, -C(O)-(C3-C 50 ) Cycloalkyl, -OC(O)-(C3-C 50 ) Cycloalkyl, -C(O)-O-(C3-C 50 ) Cycloalkyl, -C(O)- (C6-C 50 ) Aryloxy, -OC(O)-(C6-C 50 ) Aryloxy, -C(O)-O-(C6-C 50 ) Aryloxy, -C(O)-NH-(C1-C 30 ) Alkyl, -C(O)-NH-(C3-C 50 ) Cycloalkyl, -C(O)-NH-(C6-C 50 ) Aryl, -(C1-C 30 ) Alkylene-phosphoric acid, -(C3-C 50 ) Cycloalkylene-phosphoric acid, -(C6-C 50 ) Arylene-phosphoric acid. Here, one or more hydroxyl groups, carboxyl groups, amino groups, and phosphoric acid groups contained in each of R8 are optionally protected with terminal protecting groups.

[0272] Here each R 10 ’ is independently selected from the group consisting of. Hydroxyl, C(O)OH, -P(O)2-OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C1-C 30 ) Alkylene-OH, -(C3-C 50 ) Cycloalkylene-OH, -(C6-C 50 ) Arylene-OH, -(C5-C 50 ) Heteroarylene-OH, -(C1-C 30 ) Alkylene-C(O)OH, -(C3-C 50 ) Cycloalkylene-C(O)OH, -(C6-C 50 ) Arylene-C(O)OH, -(C5-C 50 ) Heteroarylene- C(O)OH, -C(O)-NH-(C1-C 30 ) Alkylene-OH, -C(O)-NH-(C3-C 50 ) Cycloalkylene-OH, -C(O)-NH-(C6-C 50)Arylene-OH, -C(O)-NH-(C5-C 50 )Heteroarylene-OH, -C(O)-NH-(C1-C 30 )Alkylene-C(O)OH, -C(O)-NH-(C3-C 50 )Cycloalkylene-C(O)OH, -C(O)-NH-(C6-C 50 )Arylene-C(O)OH, -C(O)-NH-(C5-C 50 )Heteroarylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C1-C 30 )Alkylene-C(O)OH, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-C(O)NH2, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-C(O)OH, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene- NH2, -(C1-C 30 )Alkylene-O-C(O)-(C1-C 30 )Alkylene-OH, -(C1-C 30 )Alkylene-C(O)-NH-(C3-C 50 )Cycloalkylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C6-C 50 )Arylene-C(O)OH, -(C1-C 30 )Alkylene-C(O)-NH-(C5-C 50 )Heteroarylene-C(O)OH, -(C1-C 30 )Alkylene-P(O)2-OH, -(C3-C 50 )Cycloalkylene-P(O)2-OH, -(C6-C 50 )Arylene-P(O)2-OH, -(C5-C 50 )Heteroarylene-P(O)2-OH, -C(O)-NH-(C1-C 30 )Alkylene-O-P(-N(C1-C 16 Alkyl)2)-O-(C1-C 30) alkylene-CN, -C(O)-NH-(C1-C 30 ) alkylene-OP(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-OH, -C(O)-NH-(C1-C 30 ) alkylene-OP(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-C(O)OH, -C(O)-NH-(C1-C 30 ) alkylene-OP(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-NH2, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-OP(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-CN, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-OP(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-OH, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-OP(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-C(O)OH, -(C1-C 30 ) alkylene-C(O)-NH-(C1-C 30 ) alkylene-OP(-N(C1-C 16 alkyl)2)-O-(C1-C 30 ) alkylene-NH2, -(C1-C 30 ) alkylene -P(O)-OH, -(C3-C 50 )Cycloalkylene-P(O)-OH, -(C6-C 50 ) arylene-P(O)-OH, -(C5-C 50 )-heteroarylene-P(O)-OH, -(C-C 30 ) alkylene-P(O)(S)-OH,-(C3-C50 )Cycloalkylene-P(O)(S)-OH,-(C6-C 50 )Arylene-P(O)(S)-OH,-(C5-C 50 )Heteroarylene-P(O)(S)-OH,-(C1-C 30 )Alkylene-CN, -(C3-C 50 )Cycloalkylene-CN, -(C6-C 50 )Arylene-CN, -(C5-C 50 )Heteroarylene-CN, wherein one or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in R 10 ’ are optionally protected by Rp or attached to a support material as defined herein.

[0273] In another specific embodiment, the oligonucleotide delivery enhancing compound has a structure represented by the following.

[0274]

Chemical formula

[0275]

Chemical formula

[0276]

Chemical formula

[0277]

Chemical formula

[0278]

Chemical formula

[0279]

Chemical formula

[0280]

Chem.

[0281]

Chem.

[0282]

Chem.

[0283]

Chem.

[0284]

Chem.

[0285]

Chem.

[0286]

Chem.

[0287]

Chem.

[0288]

Chem.

[0289]

Chem.

[0290]

Chem.

[0291]

Chem.

[0292]

Chem.

[0293]

Chem.

[0294]

Chem.

[0295]

Chem.

[0296]

Chem.

[0297]

Chem.

[0298]

Chem.

[0299]

Chem.

[0300]

Chem.

[0301] [Chemical]

[0302] [Chemical]

[0303] Here, [Chemical] represents a support material.

[0304] In another specific embodiment, at least one hydrogen atom contained in the oligonucleotide delivery enhancing compound is replaced with a deuterium atom.

[0305] In another specific embodiment, the present disclosure provides an oligonucleotide delivery agent comprising a delivery enhancing compound (DEC) moiety derivable from the oligonucleotide delivery enhancing compounds shown herein and at least one oligonucleotide.

[0306] In another specific embodiment, the oligonucleotide delivery enhancing compound moiety is attached to the oligonucleotide via at least one linking moiety selected from the group consisting of direct bonds, -O-, -S-, -C(O)-, -NH-, -N((C1-C 12 )alkyl)-, -N((C1-C 12 )alkyl)-C(O)-O-, -O-C(O)-,-C(O)-O-, -O-C(O)-O-,-C(O)-NH-, -OP(O)2O-,-OP(O)O-, -OP(O)(S)O-, -O-S(O)2-O-,-S(O)2-O-, -S(O)-O-,-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-, -NH-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-C(O)-, -(C1-C 22) alkylene-C(O)-, -(C1-C 22 ) alkylene-C(O)-O-, -C(O)-(C1-C 22 ) alkylene-, -NH-C(O)-(C1-C 22 ) alkylene-, -C(O)-NH-(C1-C 22 ) alkylene-, -C(O)-(C1-C 22 ) alkylene-NH-, -NH-(C1-C 22 ) alkylene-C(O)-, -C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-(C1-C 22 ) alkylene-NH-, -C(O)-(C1-C 22 ) alkylene-C(O)O-, -O-C(O)-(C1-C 22 ) alkylene-C(O)-O-, -C(O)-O-(C1-C 22 ) alkylene-O-C(O)-, -C(O)-(C1-C 22 ) alkylene-NH-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-, -NH-C(O)-(C1-C 22 ) alkylene-C(O)-NH-, -NH-(C1-C 22 ) alkylene-OP(O)2O-, -NH-(C 1 -C 22 ) alkylene-CH((C1-C 22 ) alkylene-OH)-OP(O)2O-, -NH-(C1-C 22 ) alkylene-CH((C 1 -C 22 ) alkylene-OH)-(C1-C 22 ) alkylene-OP(O)2O-, -C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-, -(C1-C 22 ) alkylene-OP(O)2O-, -(C1-C 22 ) alkylene-OP(O)O-, -(C1-C 22 ) alkylene-OP(O)(S)O-,-(C1-C 22) alkylene-O-S(O)2-O-, -(C1-C22) alkylene-S(O)2-O-, -(C1-C22) alkylene-S(O)-O-, -O-P(O)2-O-(C1-C 22 ) alkylene-OP(O)2O-, -O-P(O)-O-(C1-C 22 ) alkylene-OP(O)O-, -OP(O)(S)O-(C1-C 22 ) alkylene-OP(O)(S)O-,-O-S(O)2-O-(C1-C 22 ) alkylene-O-S(O)2-O-, -S(O)2-O-(C1-C 22 ) alkylene-S(O)2-O- and -O-S(O)-(C1-C 22 ) alkylene-S(O)-O-; and / or wherein the delivery enhancing compound (DEC) moiety is derived from an oligonucleotide delivery enhancing compound according to any one of claims 1 to 9 and is linked directly or indirectly to at least one oligonucleotide.

[0307] In another specific embodiment, the oligonucleotide comprises at least a part of the sequences set forth in SEQ ID NOs: 1 to 53.

[0308] In another specific embodiment, the oligonucleotide delivery agent comprises a structure represented by formula AA.

[0309]

Chemical formula

[0310] In another specific embodiment, the DEC is linked to the oligonucleotide via at least one first linking moiety.

[0311] In another specific embodiment, the TM is connected to the DEC via at least one second connecting portion.

[0312] In another specific embodiment, each of the first connecting portion and the second connecting portion is independently selected from the group consisting of direct bonds, -O-, -S-, -C(O)-, -NH-, -N((C1-C 12 )alkyl)-, -N((C1-C 12 )alkyl)-C(O)-O-, -O-C(O)-,-C(O)-O-, -O-C(O)-O-,-C(O)-NH-, -OP(O)2O-,-OP(O)O-, -OP(O)(S)O-, -O-S(O)2-O-,-S(O)2-O-, -S(O)-O-,-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-, -NH-(C1-C 22 )alkylene-, -(C1-C 22 )alkylene-NH-C(O)-, -(C1-C 22 )alkylene-C(O)-, -(C1-C 22 )alkylene-C(O)-O-, -C(O)-(C1-C 22 )alkylene-, -NH-C(O)-(C1-C 22 )alkylene-, -C(O)-NH-(C1-C 22 )alkylene-, -C(O)-(C1-C 22 )alkylene-NH-, -NH-(C1-C 22 )alkylene-C(O)-, -C(O)-(C1-C 22 )alkylene-C(O)-, -NH-(C1-C 22 )alkylene-NH-, -C(O)-(C1-C 22 )alkylene-C(O)O-, -O-C(O)-(C1-C 22 )alkylene-C(O)-O-, -C(O)-O-(C1-C 22 )alkylene-O-C(O)-, -C(O)-(C1-C 22 )alkylene-NH-C(O)-, -NH-C(O)-(C1-C 22 )alkylene-C(O)-, -NH-C(O)-(C1-C22 ) alkylene-C(O)-NH-, -NH-(C1-C 22 ) alkylene-OP(O)2O-, -NH-(C1-C 22 ) alkylene-CH((C1-C 22 ) alkylene-OH)-OP(O)2O-, -NH-(C1-C 22 ) alkylene-CH((C1-C 22 ) alkylene-OH)-(C1-C 22 ) alkylene-OP(O)2O-, -C(O)-NH-(C1-C 22 ) alkylene-NH-C(O)-, -(C1-C 22 ) alkylene-OP(O)2O-, -(C1-C 22 ) alkylene-OP(O)O-, -(C1-C 22 ) alkylene-OP(O)(S)O-,-(C1-C 22 ) alkylene-O-S(O)2-O-, -(C1-C 22 ) alkylene-S(O)2-O-, -(C1-C 22 ) alkylene-S(O)-O-, -O-P(O)2-O-(C1-C 22 ) alkylene-OP(O)2O-, -O-P(O)-O-(C1-C 22 ) alkylene-OP(O)O-, -OP(O)(S)O-(C1-C 22 ) alkylene-OP(O)(S)O-,-O-S(O)2-O-(C1-C 22 ) alkylene-O-S(O)2-O-, -S(O)2-O-(C1-C 22 ) alkylene-S(O)2-O- and -O-S(O)-(C1-C 22 ) alkylene-S(O)-O-; and / or wherein the oligonucleotide is selected from the group consisting of short interfering RNA (siRNA), small activating RNA (saRNA), microRNA (miRNA), antisense oligonucleotide (ASO), and small guide RNA (sgRNA).

[0313] In another specific embodiment, the targeting moiety is one or more selected from the group consisting of a ligand, a peptide, a nucleic acid, an oligonucleotide, an aptamer, a lipid, a fatty acid, a small molecule, polyethylene glycol, an amino acid, cholesterol, a carbohydrate, and an antibody or antibody fragment.

[0314] In another specific embodiment, the oligonucleotide delivery agent has a structure represented by any of Formulas AAI to AAXXIV:

[0315]

Chemical Formula

[0316]

Chemical Formula

[0317] Here, L represents a linking moiety,

Chemical Formula

Chemical Formula

Chemical Formula

[0318] In another specific embodiment, at least one hydrogen atom contained in the delivery enhancing compound moiety, the linking moiety, the targeting moiety, and / or the oligonucleotide is replaced with a deuterium atom.

[0319] In another specific embodiment, the present disclosure provides a pharmaceutical composition, which composition comprises: a) an oligonucleotide delivery agent as shown herein, and b) optionally, one or more components selected from the group consisting of pharmaceutically acceptable carriers, excipients, solvents, diluents, stabilizers, dispersants, buffers, solubilizers, preservatives, and combinations thereof.

[0320] In another specific embodiment, the present disclosure provides a method for regulating the expression of a target gene in a subject, the method comprising administering to the subject a pharmaceutical composition as shown herein.

[0321] In another specific embodiment, the oligonucleotide or the target gene comprises at least a part of the sequences set forth in SEQ ID NOs: 1-53.

[0322] In another specific embodiment, the pharmaceutical composition increases the expression of the target gene. In another specific embodiment, the pharmaceutical composition decreases the expression of the target gene. In another specific embodiment, the subject is a mammal. In another specific embodiment, the mammal is a rodent. In another specific embodiment, the rodent is a mouse. In another specific embodiment, the rodent is a rat. In another specific embodiment, the mammal is a non-human primate. In another specific embodiment, the mammal is a human. In another specific embodiment, the target gene is associated with a disease or disorder. In another specific embodiment, the target gene is associated with a disease or disorder in the central nervous system (CNS), brain, spinal cord, liver, lung, kidney, intestine, pancreas, gallbladder, heart, lymph node, spleen, stomach, bladder, muscle or bone. In another specific embodiment, the disease is cancer.

[0323] In another specific embodiment, the present disclosure provides a method for regulating the expression of a target gene, the method comprising contacting a cell with a pharmaceutical composition as shown herein.

[0324] In another specific embodiment, the oligonucleotide or the target gene comprises at least a part of the sequences set forth in SEQ ID NOs: 1-53.

[0325] In another specific embodiment, the pharmaceutical composition increases the expression of the target gene. In another specific embodiment, the pharmaceutical composition decreases the expression of the target gene. In another specific embodiment, the cell is a mammalian cell. In another specific embodiment, the mammalian cell is a mouse cell. In another specific embodiment, the mammalian cell is a rat cell. In another specific embodiment, the mammalian cell is a non-human primate cell. In a specific embodiment, the mammalian cell is a human cell. In another specific embodiment, the target gene is associated with a disease or disorder. In another specific embodiment, the target gene is associated with a disease or disorder in the central nervous system (CNS), brain, spinal cord, liver, lung, kidney, intestine, pancreas, gallbladder, heart, lymph node, spleen, stomach, bladder, muscle or bone. In another specific embodiment, the disease is cancer.

Examples

[0326] Some embodiments of the present invention are described in the following examples, where all parts and percentages are by weight unless otherwise specified. However, the scope of the present disclosure is, of course, not limited to the formulations described in these examples. Rather, the examples are merely the invention disclosed.

[0327] The following examples are set forth to provide a complete disclosure and description to those skilled in the art of the methods of making and using the invention, and are not intended to limit the scope of what the inventors regard as their invention, nor are they intended to represent that the following experiments are all or the only experiments. Efforts have been made to ensure accuracy with respect to the numerical values used (e.g., amounts, temperatures, etc.), but some experimental error and deviation should be accounted for. Unless otherwise noted, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric pressure. Standard abbreviations may be used. For example, bp is base pair, kb is kilobase, nM is nanomole, s or sec is second, min is minute, h or hr is hour, aa is amino acid, nt is nucleotide, i.m. is intramuscular, i.p. is intraperitoneal, s.c. is subcutaneous, ivt or IVT is intravitreal, iv or IV is intravenous, tail vein, i.c.v. or icv or ICV is intracerebroventricular, etc.

[0328] All starting materials, reagents, and solvents used hereinafter were purchased from commercial sources and used as received, unless otherwise specified. Purification of the reaction products was carried out using column chromatography with silica gel (200 - 300 mesh) and eluents of hexane / ethyl acetate, DCM / MeOH. Thin layer chromatography (TLC) was performed using pre-coated silica gel GF plates and visualized by KMnO4 staining. 1H-NMR spectra were recorded at 400 or 500 MHz (Varian) using CDCl3 solutions containing TMS as the standard. High resolution mass spectra (HRMS) were recorded by ESI or MALDI (matrix-assisted laser desorption ionization) using LC / MS (Agilent Technologies 1260 Infinity II / 6120 Quadrupole) and a time-of-flight mass spectrometer.

[0329] Example 1: Preparation of Compound A1 of the present disclosure In this example, Compound A1 was prepared according to the following procedure.

[0330]

Chemical formula

[0331] (1) Preparation of Compound A62

[0332]

Chem.

[0333] To a solution of Fmoc-L-hydroxyproline A61 (13.3 g, 37.6 mmol, 1.0 eq) in anhydrous THF (250 mL) was slowly added borane-methyl sulfide complex (8.0 mL of 10 M in THF, 80 mmol, 2.1 eq) at room temperature. The reaction mixture was stirred at room temperature for 5 minutes and then heated to reflux for about 1 hour. Methanol (15 mL) was carefully added to the reaction mixture, and after refluxing for 15 minutes, the reaction mixture was concentrated under reduced pressure. Then, the crude product was evaporated three times with methanol (100 mL each). The crude product A62 was used directly in the next step without further purification.

[0334] (2) Preparation of Compound A63

[0335]

Chem.

[0336] To a solution of compound A62 (37.6 mmol, 1.0 eq) in anhydrous pyridine (200 mL), DMTrCl (14 g, 41.4 mmol, 1.1 eq) was slowly added under an ice bath. After the reaction mixture was stirred overnight under a nitrogen atmosphere, it was concentrated under reduced pressure. The crude product was dissolved in dry MeCN (300 mL), Et3N (15.6 mL, 113 mmol, 3.0 eq) was added to the mixture, and the mixture was heated at 60 °C for 4 h. After concentration under reduced pressure, the obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 8% MeOH / DCM) to obtain the desired product A63 (7.57 g, yield 48%) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 419.21; MW Found: 303.2 [DMT] - . 1 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.4 Hz, 2H), 7.30 (d, J = 8.8 Hz, 4H), 7.28 - 7.22 (m, 2H), 7.18 (t, J = 7.2 Hz, 1H), 6.80 (d, J = 8.8 Hz, 4H), 4.34 (s, 1H), 3.75 (d, J = 11.1 Hz, 6H), 3.60 (dd, J = 12.7, 6.7 Hz, 1H), 3.10 - 2.92 (m, 5H), 2.86 (d, J = 11.5 Hz, 1H), 1.85 (dd, J = 13.5, 7.1 Hz, 1H), 1.63 (ddd, J = 13.7, 7.9, 5.9 Hz, 1H). (3) Preparation of compound A66

[0337]

Chemical Structure

[0338] To a solution of compound A64 (1.4 g, 7.2 mmol, 2.0 eq) in DCM (30 mL) under a nitrogen atmosphere, compound A65 (1.0 g, 3.6 mmol, 1.0 eq), O-benzotriazol-1-yl-N, N, N', N'-tetramethyluronium hexafluorophosphate (HBTU) (2.7 g, 7.2 mmol, 2.0 eq) and N,N-diisopropylethylamine (DIPEA) (0.93 g, 7.2 mmol, 2.0 eq) were added. The reaction mixture was stirred at room temperature overnight. Next, 30 mL of H2O was added to the reaction mixture, and the mixture was extracted with DCM (3 × 30 mL). The organic phases were combined, dried over Na2SO4 and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1-5% MeOH / DCM) to give compound A66 (1.7 g, 94% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 453.31; MW Found: 454.29 [M+H] + . 1 H NMR (400 MHz, CDCl3) δ3.69 - 3.61 (m, 5H), 3.59 - 3.53 (m, 8H), 3.48 (t, J = 5.2 Hz, 2H), 3.35 (dd, J = 10.7, 5.3 Hz,2H), 3.15 (qd, J = 7.4, 4.4 Hz, 3H), 2.43 (t, J = 6.4 Hz, 2H), 1.92 - 1.85 (m, 5H), 1.54 - 1.52 (m,4H), 1.37 (s, 12H). (4) Preparation of compound A67

[0339]

Chemical Structure

[0340] To a solution of Compound A66 (0.8 g, 1.7 mmol, 1.0 eq) in DCM (10 mL) was added HCl / dioxane (4 M 10 mL). The reaction mixture was stirred at room temperature for 3 h and then concentrated under reduced pressure to give the crude product as a yellow oil. The crude product was dissolved in DCM (10 mL), and then Compound A63 (583 mg, 1.7 mmol, 1.0 eq), HBTU (1.28 g, 3.4 mmol, 2.0 eq) and DIPEA (439 mg, 3.4 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Next, 10 mL of H2O was added to the reaction mixture and the mixture was extracted with DCM (3 × 20 mL). The organic phases were combined, dried over Na2SO4 and concentrated. The residue obtained was purified by flash chromatography (silica gel, gradient eluent: 10% MeOH / DCM) to give Compound A67 (261 mg, yield 21%) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 798.45; MW Found: 303.31 [DMT] - , 519.62 [DMT off + Na] + . 1 HNMR (400 MHz, CDCl3) δ 7.36 (d, J = 7.7 Hz, 2H), 7.26 -7.23 (m, 6H), 7.17 (t, J=7.0 Hz, 1H), 6.81 (dd, J = 11.4, 5.1 Hz,4H), 3.85 - 3.81 (m, 1H), 3.77 (s, 6H), 3.62 - 3.56 (m,8H), 3.53 (dd, J = 9.1, 4.5 Hz, 2H), 3.44 -3.32 (m, 4H), 2.73 (q, J=7.2 Hz, 6H), 2.45 - 2.33 (m, 1H), 2.26 - 2.16 (m, 1H), 2.15 - 2.02 (m,1H), 1.99 - 1.90 (m, 5H), 1.72 - 1.66 (m, 3H), 1.63 - 1.58 (m,9H). (5) Preparation of Compound A68

[0341]

Chemical Structure

[0342] To a solution of Compound A67 (666 mg, 0.92 mmol, 1.0 eq) and DMAP (393 mg, 3.22 mmol, 3.5 eq) in DCM (6 mL) was added succinic anhydride (282 mg, 2.76 mmol, 3.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight and then H2O (10 mL) was added to the reaction. The mixture was extracted with DCM (3 × 10 mL). The combined organic phases were dried over Na2SO4 and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to give Compound A68 (447 mg, 59% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 898.46; MW Found: 303.15 [DMT] - , 597.98 [DMT off + H] + . 1 HNMR (400 MHz, CDCl3) δ 7.36 - 7.32 (m, 2H), 7.27 - 7.25 (m, 6H), 7.19 - 7.16 (m,1H), 6.85 - 6.76 (m, 4H), 5.46 - 5.32 (m, 1H), 3.82 (d, J = 6.3Hz, 1H), 3.77 (s, 6H), 3.60 (dd,J = 9.3, 4.5 Hz, 8H), 3.53 (t, J = 5.0 Hz,2H), 3.44 - 3.40 (m, 2H), 3.14 (dd, J = 9.2, 2.9 Hz, 1H), 2.99 - 2.93 (m, 6H), 2.62 - 2.45 (m,5H), 2.34 - 2.28 (m, 1H), 2.19 - 2.04 (m, 1H), 1.96 - 1.92 (m,5H), 1.69 - 1.66 (m, 3H), 1.62 - 1.58 (m, 9H). (6) Preparation of Compound A1

[0343]

Chemical formula

[0344] To a solution of Compound A68 (200 mg, 0.223 mmol, 1.0 eq) in acetonitrile (30 mL), controlled pore glass (CPG) (3.9 g), and DIPEA (111 μL, 0.669 mmol, 3.0 eq) was added HBTU (169 mg, 0.446 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed successively with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (12 mL), pyridine (28 mL), and NEt3 (401 μL) in acetonitrile (18 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed successively with DCM and ethyl ether to produce Compound A1 (3.67 g) of the present disclosure.

[0345] Example 2: Preparation of Compound A2 of the Present Disclosure In this example, Compound A2 was prepared by the following procedure.

[0346]

Chemical formula

[0347] (1) Preparation of Compound A70

[0348]

Chemical formula

[0349] To a solution of methyl 4-fluoro-3-nitrobenzoate A69 (8.0 g, 40.2 mmol, 1.0 eq) and K2CO3 (5.5 g, 40.2 mmol) in anhydrous DMF (100 mL) was added benzyl (3-aminopropyl)carbamate (8.3 g, 40.2 mmol, 1.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C for 6 h, then cold water (100 mL) was added. The mixture was extracted three times with ethyl acetate, and the organic phase was washed three times with saturated lithium chloride solution and once with brine. It was then dried over anhydrous Na2SO4 and concentrated under reduced pressure to form a yellow solid (compound A70). This solid was used directly in the next step without further purification.

[0350] (2) Preparation of Compound A72

[0351]

Chemical formula

[0352] To a solution of compound A70 (10 g, 25.84 mmol, 1.0 eq) in THF / H2O (9:1, 100 mL) was added HCOONH4 (9.78 g, 155.04 mmol, 6.0 eq) and Zn powder (10.14 g, 155.04 mmol, 6.0 eq) under an ice bath. After 10 min, the reaction mixture was transferred to room temperature and stirred overnight. The reaction mixture was then filtered and concentrated under reduced pressure. Thereafter, water (100 mL) was added to the mixture, and it was extracted three times with ethyl acetate, and the organic phase was washed once with brine. After drying over anhydrous Na2SO4 and concentrating under reduced pressure, the resulting light red solid compound A72 was used directly in the next step without further purification.

[0353] (3) Preparation of Compound A73

[0354]

Chemical formula

[0355] To a solution of compound A72 (8.0 g, 22.5 mmol, 1.0 eq) in EtOH (200 mL), 3-((tert-butyldimethylsilyl)oxy)propanal (4.2 g, 22.5 mmol, 1.0 eq) and AcOH (5.1 mL, 90 mmol, 4.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then saturated NaHCO3 solution (100 mL) was added, and the mixture was extracted three times with ethyl acetate. Then the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue, compound A73, was used directly in the next step without further purification. This compound A73 was characterized by mass spectrometry. MW calc: 525.27; MW.Found: 526.59 [M+H] + . (4) Preparation of compound A74

[0356]

Chemical formula

[0357] To a solution of compound A73 (5.0 g, 9.5 mmol, 1.0 eq) in anhydrous THF (50 mL), 1 M TBAF THF solution (14.25 mL, 14.25 mmol, 1.5 eq) was added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. Then water (100 mL) was added, and the mixture was extracted three times with DCM. The organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue was dissolved in 50 mL of pyridine, and DMTrCl (3.86 g, 11.4 mmol, 1.2 eq) was added. The reaction mixture was stirred at room temperature for 6 hours and then concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A74 (4.1 g, 60% yield) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 713.31; MW Found: 303.17 [DMT]-, 412.36 [DMT off + H] + . 1HNMR (400 MHz, CDCl3) δ 8.39 (d, J = 1.1 Hz, 1H), 7.96 (dd, J = 8.5, 1.3 Hz, 1H), 7.38 - 7.27 (m, 8H), 7.20 (dq, J = 6.7, 2.5 Hz, 7H), 6.76 - 6.70 (m, 4H), 5.10 (s, 2H), 4.19 (t, J = 7.3 Hz, 2H), 3.94 (s, 3H), 3.74 (s, 6H), 3.65 (t, J = 6.6 Hz, 2H), 3.20 (d, J = 6.3 Hz, 2H), 3.09 (t, J = 6.4 Hz, 2H), 2.00 - 1.90 (m, 2H). (5) Preparation of Compound A75

[0358] [Chemical formula]

[0359] To a solution of Compound A74 (4.0 g, 5.6 mmol, 1.0 eq) in anhydrous THF (50 mL), LiAlH4 (319 mg, 8.4 mmol, 1.5 eq) was added under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction mixture was transferred to an ice bath, and saturated sodium potassium tartrate solution (30 mL) was slowly added. After 30 minutes, the reaction mixture was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue was dissolved in 50 mL of DMF, and then imidazole (572 mg, 8.4 mmol, 1.5 eq) and TBSCl (1.27 g, 8.4 mmol, 1.5 eq) were added. After stirring the reaction mixture at room temperature for 1 hour, it was concentrated under reduced pressure, and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain Compound A75 (4.03 g, yield 90%) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 799.40; MW.Found: 303.17 [DMT]. 11H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.38 - 7.29 (m,7H), 7.19 (ddd, J = 8.4, 7.9, 3.7 Hz, 9H), 6.78-6.71 (m, 4H), 5.10 (s,2H), 4.84 (s, 2H), 4.16 (t,J = 7.2 Hz, 2H), 3.75 (s, 6H), 3.61 (t, J = 6.8 Hz, 2H), 3.18 (d,J = 6.3 Hz, 2H), 3.07 (t, J = 6.4 Hz, 2H), 2.95 (s, 1H), 2.88 (s, 1H),0.94 (s, 9H), 0.10 (s,6H). (6) Preparation of Compound A78

[0360]

Chem.

[0361] To a solution of compound A75 (220 mg, 0.276 mmol, 1.0 eq) in MeOH (8 mL) was slowly added Pd / C (22 mg) under a nitrogen atmosphere. Next, the reaction atmosphere was replaced with hydrogen three times. Then, the reaction mixture was purged with a hydrogen balloon and stirred at room temperature overnight. Subsequently, the reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (8 mL), and then compound A77 (64 mg, 0.33 mmol, 1.2 eq), HBTU (209 mg, 0.552 mmol, 2.0 eq), and DIPEA (155 μL, 0.938 mmol, 3.4 eq) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Then, H2O (10 mL) was added to the reaction, and the mixture was extracted three times with DCM (3 * 10 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A78 (199 mg, 86% yield) as a yellow oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 841.48; MW Found: 303.2 [DMT] -, 540.3 [DMT off + H] + . 1 HNMR (400 MHz, CDCl3) δ 7.65(s, 1H), 7.38 - 7.29 (m,7H), 7.19 (ddd, J = 8.4, 7.9, 3.7 Hz, 9H), 6.78 -6.71 (m, 4H), 5.10 (s,2H), 4.84 (s, 2H), 4.16 (t,J = 7.2 Hz, 2H), 3.75 (s, 6H), 3.61 (t, J = 6.8 Hz, 2H), 3.18 (d,J = 6.3 Hz, 2H), 3.07 (t, J = 6.4 Hz, 2H), 2.95 (s, 1H), 2.88 (s, 1H),0.94 (s, 9H), 0.10 (s,6H). (7) Preparation of Compound A79

[0362] [Chemical formula]

[0363] To a solution of compound A78 (165 mg, 0.196 mmol, 1.0 eq) in anhydrous THF (5 mL) was added 1M TBAF THF solution (1.18 mL, 1.18 mmol, 6.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (8 mL), and DMAP (84 mg, 0.686 mmol, 3.5 eq) and succinic anhydride (39 mg, 0.392 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, and the mixture was extracted with DCM (3 × 10 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 8% MeOH / DCM) to obtain compound A79 (97 mg, 60% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc:827.41; MW Found: 303.2 [DMT] -, 527.3 [DMT off + H] + . 1 HNMR (400 MHz, CDCl3) δ 7.65(s, 1H), 7.38 - 7.29 (m,7H), 7.19 (ddd, J = 8.4, 7.9, 3.7 Hz, 9H), 6.78 -6.71 (m, 4H), 5.10 (s,2H), 4.84 (s, 2H), 4.16 (t,J = 7.2 Hz, 2H), 3.75 (s, 6H), 3.61 (t, J = 6.8 Hz, 2H), 3.18 (d,J = 6.3 Hz, 2H), 3.07 (t, J = 6.4 Hz, 2H), 2.95 (s, 1H), 2.88 (s, 1H),0.94 (s, 9H), 0.10 (s,6H). (8) Preparation of Compound A2

[0364]

Chem.

[0365] To a solution of Compound A79 (85 mg, 0.103 mmol, 1.0 eq), controlled pore glass (CPG) (1.8 g), and DIPEA (51 μL, 0.31 mmol, 3.0 eq) in acetonitrile (14 mL) was added HBTU (78 mg, 0.206 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed successively with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (6.2 mL), pyridine (12 mL), and NEt3 (186 μL) in acetonitrile (7.9 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed successively with DCM and ethyl ether to obtain Compound A1 (1.62 g) of the present disclosure.

[0366] Example 3: Preparation of Compound A3 of the Present Disclosure In this example, Compound A3 of the present disclosure was prepared by the following procedure.

[0367]

Chem.

[0368] (1) Preparation of Compound A81

[0369] [Chemical formula]

[0370] To a solution of compound A75 (1.44 g, 1.8 mmol, 1.0 eq) in MeOH (30 mL) was slowly added Pd / C (144 mg) under a nitrogen atmosphere. Next, the reaction atmosphere was replaced with hydrogen three times. Then, the reaction mixture was purged with a hydrogen balloon and stirred at room temperature overnight. The reaction mixture was then filtered and concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (40 mL), and then palmitic acid (508 mg, 1.98 mmol, 1.1 eq), HBTU (1.36 g, 3.6 mmol, 2.0 eq), and DIPEA (1.01 mL, 6.12 mmol, 3.4 eq) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Then, H2O (30 mL) was added to the reaction, and the mixture was extracted three times with DCM (3 × 40 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A81 (1.43 g, 88% yield) as a yellow oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 903.59; MW Found: 303.2 [DMT] - , 488.4 [DMT and TBS off +H] + . 11H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 4.7 Hz, 1H), 7.33 - 7.27 (m, 4H), 7.22 - 7.16 (m, 7H), 6.74 (dd, J = 8.1, 5.6 Hz, 4H), 4.83 (s, 2H), 4.23 - 4.16 (m, 2H), 3.76 (s, 6H), 3.62 (dd, J = 11.9, 5.3 Hz, 2H), 3.27 - 3.21 (m, 2H), 3.15 (d, J = 6.9 Hz, 2H), 2.11 - 2.05 (m, 2H), 2.03 - 1.90 (m, 2H), 1.34 - 1.25 (m, 29H), 0.95 (s, 9H), 0.11 (s, 6H). (2) Preparation of Compound A82

[0371] [Chemical formula]

[0372] To a solution of compound A81 (1.4 g, 1.55 mmol, 1.0 eq) in anhydrous THF (30 mL) was added 1M TBAF THF solution (4.65 mL, 4.65 mmol, 3.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (40 mL), and DMAP (660 mg, 5.4 mmol, 3.5 eq) and succinic anhydride (465 mg, 4.65 mmol, 3.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (30 mL) was added to the reaction, and the mixture was extracted with DCM (3 × 30 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 8% MeOH / DCM) to obtain compound A82 (827 mg, 60% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 889.52; MW Found: 303.1 [DMT] -, 588.3 [DMT off + H] + . 1 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 4.5 Hz, 1H), 7.34 - 7.28 (m, 2H), 7.25 - 7.14 (m, 9H), 6.74 (dd, J = 8.1, 5.5 Hz, 4H), 5.21 (s, 2H), 4.34 - 3.90 (m, 2H), 3.74 (s, 6H), 3.60 (dd, J = 12.1, 5.4 Hz, 2H), 3.22 - 3.16 (m, 2H), 3.09 - 3.04 (m, 2H), 2.63 - 2.60 (m, 4H), 2.16 - 2.01 (m, 2H), 1.97 - 1.84 (m, 2H), 1.33 - 1.23 (m, 26H), 0.87 (t, J = 6.7 Hz, 3H). (3) Preparation of Compound A3

[0373]

Chemical Structure

[0374] To a solution of Compound A82 (120 mg, 0.13 mmol, 1.0 eq), controlled pore glass (CPG) (2.29 g), and DIPEA (65 μL, 0.39 mmol, 3.0 eq) in acetonitrile (15 mL) was added HBTU (99 mg, 0.26 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (7.8 mL), pyridine (15 mL), and NEt3 (234 μL) in acetonitrile (10 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce Compound A3 (2.1 g) of the present disclosure.

[0375] Example 4: Preparation of Compound A4 and Compound A5 of the Present Disclosure In this example, Compounds A4 and A5 were prepared using the following procedure.

[0376]

Chem.

[0377] (1) Preparation of Compound A85

[0378]

Chem.

[0379] To a solution of methyl 2-(4-fluoro-3-nitrophenyl)acetate A84 (17.3 g, 81 mmol, 1.0 eq) and K2CO3 (11.2 g, 81 mmol) in anhydrous DMF (000 mL) was added compound A83 (19.56 g, 81 mmol, 1.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 55 °C for 6 h, then cold water (100 mL) was added. The mixture was extracted three times with ethyl acetate, and the organic phase was washed three times with saturated lithium chloride solution and once with brine. It was then dried over anhydrous Na2SO4 and concentrated under reduced pressure to form a yellow oil (compound A85). This oil was used directly in the next step without further purification.

[0380] (2) Preparation of Compound A86

[0381]

Chem.

[0382] A solution of compound A85 (35.18 g, 81 mmol, 1.0 eq) in THF / H2O (9:1, 280 mL) was added with HCOONH4 (30.67 g, 486 mmol, 6.0 eq) and Zn powder (31.78 g, 486 mmol, 6.0 eq) under an ice bath. After 10 minutes, the reaction mixture was transferred to room temperature and stirred overnight. Then, the reaction mixture was filtered and concentrated under reduced pressure. Thereafter, water (200 mL) was added to the mixture, and the mixture was extracted three times with ethyl acetate, and the organic phase was washed once with brine. After drying over anhydrous Na2SO4 and concentrating under reduced pressure, the product 86 was used directly in the next step without further purification. This compound A86 was characterized by mass spectrometry. MW calc: 404.34; MW.Found: 405.3 [M+H] + . (3) Preparation of compound A88

[0383]

Chem.

[0384] To a solution of compound A86 (19.36 g, 48 mmol, 1.0 eq) in EtOH (200 mL) were added 3-((tert-butyldimethylsilyl)oxy)propanal A87 (9.0 g, 48 mmol, 1.0 eq) and AcOH (11 mL, 192 mmol, 4.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then, saturated NaHCO3 solution (100 mL) was added, and the mixture was extracted three times with ethyl acetate. Then, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue compound A88 was used directly in the next step without further purification.

[0385] (4) Preparation of compound A89

[0386]

Chem.

[0387] To a solution of compound A88 (10 g, 17.5 mmol, 1.0 eq) in anhydrous THF (50 mL) was added 1M TBAF THF solution (26.3 mL, 26.3 mmol, 1.5 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. Then water (100 mL) was added, and the mixture was extracted three times with DCM. The organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue was dissolved in 50 mL of pyridine, and DMTrCl (7.12 g, 21 mmol, 1.2 eq) was added. The reaction mixture was stirred at room temperature for 6 hours and then concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 3% MeOH / DCM) to obtain compound A89 (8.1 g, 61% yield) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 760.48; MW.Found: 761.8 [M + H] + . 1 H NMR (400 MHz, CDCl3) δ7.59 - 7.53 (m, 1H), 7.38 - 7.31 (m, 2H), 7.23 - 7.19 (m,6H), 7.18 - 7.14 (m, 3H), 6.76 (dd, J = 7.8, 5.6 Hz, 4H), 4.17 -4.02 (m, 2H), 3.76 (s, 6H),3.73 (s, 2H), 3.67 (s,3H), 3.59 (t, J = 7.0 Hz, 2H), 3.19 - 3.05 (m, 2H), 1.29 - 1.25 (m,28H), 0.88 (t, J = 6.5 Hz, 3H). (5) Preparation of compound A90

[0388]

Chemical Structure

[0389] To a solution of compound A89 (2.7 g, 3.55 mmol, 1.0 eq) in anhydrous THF (20 mL), LiAlH4 (202 mg, 5.33 mmol, 1.5 eq) was added under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath and saturated sodium potassium tartrate solution (20 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The crude product (300 mg, 0.41 mmol, 1.0 eq) was dissolved in DCM (10 mL), and DMAP (175 g, 1.44 mmol, 3.5 eq) and succinic anhydride (123 mg, 1.23 mmol, 3.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, the mixture was extracted with DCM (3 × 20 mL), the organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to give compound A90 (113 mg, 33% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 832.50; MW Found: 303.2 [DMT] - , 531.3 [DMT off + H] + . 1 HNMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.31 (dd, J = 7.6, 4.1 Hz, 2H), 7.28 - 7.11 (m, 9H), 6.74 (dd, J = 7.9, 5.6 Hz, 4H), 4.35 - 4.32 (m, 2H), 4.12 - 4.08 (m, 2H), 3.75 (s, 6H), 3.59 (dd, J = 11.8, 5.1 Hz, 2H), 3.24 - 3.10 (m, 2H), 3.09 - 2.96 (m, 2H), 2.63 (dd, J = 7.2, 3.0 Hz, 4H), 1.37 - 1.25 (m, 28H), 0.88 (t, J = 6.5 Hz, 3H). (6) Preparation of compound A4

[0390]

Chem.

[0391] To a solution of Compound A90 (90 mg, 0.108 mmol, 1.0 eq) in acetonitrile (14 mL), controlled pore glass (CPG) (1.89 g), and DIPEA (51 μL, 0.324 mmol, 3.0 eq) was added HBTU (82 mg, 0.216 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (6.5 mL), pyridine (12.6 mL), and NEt3 (195 μL) in acetonitrile (8.3 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce Compound A1 (1.7 g) of the present disclosure.

[0392] (7) Preparation of Compound A5

[0393]

Chem.

[0394] To a solution of compound A89 (2.7 g, 3.55 mmol, 1.0 eq) in anhydrous THF (20 mL), LiAlH4 (202 mg, 5.33 mmol, 1.5 eq) was added under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath and saturated sodium potassium tartrate solution (20 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The crude product (300 mg, 0.41 mmol, 1.0 eq) was dissolved in anhydrous DCM (5 mL), then DIPEA (204 μL, 1.23 mmol, 3.0 eq) and 3-((chloro(diisopropylamino)phosphanyl)oxy)propanenitrile (274 μL, 1.23 mmol, 3.0 eq) were added at 25 °C under a nitrogen atmosphere. The reaction mixture was stirred for 1 hour. The mixture was extracted twice with DCM, then washed with brine and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM, 1% Et3N) to give compound A5 (299 mg, 78% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 946.61; MW Found: 303.2 [DMT] - . 1 H NMR (400 MHz, CDCl3) δ7.62 (s, 1H), 7.32 (dd,J= 7.6, 4.1 Hz, 2H), 7.27 - 7.11 (m, 9H),6.73 (dd, J= 7.9, 5.6 Hz, 4H), 4.34 - 4.31 (m, 2H), 4.10 - 4.06 (m,2H), 3.75 (s, 6H), 3.64 - 3.61 (m, 2H), 3.58 (dd, J=11.8, 5.1 Hz, 2H), 3.24 - 3.18 (m, 2H), 3.09 - 2.88(m, 4H), 2.65 -2.55 (m,4H), 1.37 - 1.28 (m, 28H), 1.22 (dd, J = 6.8, 3.2 Hz, 12H), 0.88 (t, J = 6.5 Hz, 3H). Example 5: Preparation of Compound A6 of the Present Disclosure In this example, Compound A6 was prepared according to the following procedure.

[0395] [Chemical formula]

[0396] (1) Preparation of Compound A92

[0397] [Chemical formula]

[0398] To a solution of Compound A72 (8.87 g, 24.84 mmol, 1.0 eq) in EtOH (200 mL) was added 5-((tert-butyldimethylsilyl)oxy)pentanal A91 (5.4 g, 24.84 mmol, 1.0 eq) and AcOH (5.73 mL, 99.36 mmol, 4.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Next, saturated NaHCO3 solution (100 mL) was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with brine, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain Compound A92 (6.3 g, 46% yield) as a red solid. This product was characterized by mass spectrometry, 1 1H NMR, and 13 13C NMR. MW calc: 553.30; MW Found: 554.29 [M + H] + . 11H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 0.8 Hz, 1H), 7.95 (dd, J = 8.5, 1.1 Hz, 1H), 7.44 - 7.28 (m, 5H), 7.26 (d, J = 6.8 Hz, 1H), 5.12 (s, 2H), 4.16 (dd, J = 12.6, 5.3 Hz, 2H), 3.93 (s, 3H), 3.67 (t, J = 6.3 Hz, 2H), 3.28 (d, J = 6.2 Hz, 2H), 2.87 (t, J = 7.6 Hz, 2H), 2.04 - 1.88 (m, 4H), 1.67 (dd, J = 14.7, 6.6 Hz, 2H), 0.88 (s, 9H), 0.04 (s, 6H). 13 13C NMR (100 MHz, CDCl3) δ 167.72, 156.63, 142.35, 138.19, 136.30, 128.60, 128.24, 124.10, 123.87, 121.63, 108.66, 66.96, 62.71, 60.41, 52.06, 41.31, 38.57, 32.46, 30.43, 27.30, 25.97, 24.15, 21.07, 18.34, 14.21. (2) Preparation of Compound A93

[0399]

Chemical Structure

[0400] To a solution of compound A92 (6.3 g, 11.4 mmol, 1.0 eq) in anhydrous THF (50 mL) was added 1M TBAF THF solution (26.3 mL, 17.1 mmol, 1.5 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. Then water (100 mL) was added, and the mixture was extracted 3 times with DCM. The organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue was dissolved in 50 mL of pyridine, and DMTrCl (4.6 g, 13.68 mmol, 1.2 eq) was added. The reaction mixture was stirred at room temperature for 6 hours and then concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A93 (6.23 g, yield 74%) as a yellow solid. This product was characterized by mass spectrometry, 1 1H NMR and 13 13C NMR. MW calc: 741.34; MW.Found: 303.11 [DMT]-, 440.14 [DMT off + H] + . 1 1H NMR (400 MHz, CDCl3) δ 8.63 (dd, J = 5.7, 1.5 Hz, 1H), 8.43 (d, J = 1.0 Hz, 1H), 7.97 (dd,J = 8.5, 1.1 Hz, 1H), 7.45 (d, J = 7.4 Hz, 2H),7.37 - 7.28 (m, 11H), 7.21 (dd,J = 8.1, 6.1 Hz, 1H), 6.83 (t, J = 5.9 Hz, 4H),5.13 (s, 2H), 4.12 (t,J = 7.2 Hz, 2H), 3.95 (s, 3H), 3.79 (s, 6H), 3.24 (d, J = 6.2Hz, 2H), 3.14 (t, J = 6.2 Hz, 2H), 2.83 (t, J = 7.4 Hz, 2H), 2.01 (dd,J = 16.0, 8.5 Hz, 4H), 1.79 (dd, J = 14.1, 6.6 Hz,2H). 1313C NMR (100 MHz, CDCl3) δ 167.81, 158.43, 156.64, 149.95, 145.34, 142.43, 138.26, 136.57, 136.05, 130.11, 128.69, 128.39, 128.26, 128.23, 127.84, 126.75, 124.17, 123.89, 121.70, 113.11, 108.75, 85.93, 67.02, 62.90, 55.31, 52.16, 41.37, 38.64, 30.50, 29.76, 27.30, 24.53. (3) Preparation of Compound A94

[0401] [Chemical formula]

[0402] To a solution of Compound A93 (5.0 g, 6.74 mmol, 1.0 eq) in anhydrous THF (20 mL), LiAlH4 (384 mg, 10.11 mmol, 1.5 eq) was added under a nitrogen atmosphere and an ice bath. Then, the mixture was transferred to room temperature after 10 minutes and stirred for about 1 hour. Next, the reaction mixture was transferred to an ice bath, and a saturated aqueous solution of sodium potassium tartrate (30 mL) was slowly added. After reacting for 30 minutes, the reaction mixture was extracted three times with Et2O. The combined organic phases were washed with brine, dried over Na2SO4, and concentrated. The resulting residue was dissolved in 20 mL of DMF, and then imidazole (688 mg, 10.11 mmol, 1.5 eq) and TBSCl (1.524 g, 10.11 mmol, 1.5 eq) were added. After stirring the reaction mixture at room temperature for 1 hour, it was concentrated under reduced pressure, and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain Compound A94 (4.78 g, yield 86%) as a yellow solid. This product was characterized by mass spectrometry, 1 1H NMR and 13 13C NMR. MW calc: 827.43; MW.Found: 303.16 [DMT]-, 526.50 [DMT off + H] + . 11H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.47 - 7.42 (m, 2H), 7.40 - 7.28 (m, 11H), 7.22 (t, J = 3.5 Hz, 3H), 6.86 - 6.80 (m, 4H), 5.13 (s, 2H), 4.86 (s, 2H), 4.15 (dd, J = 14.3, 7.2 Hz, 2H), 3.79 (s, 6H), 3.13 (t, J = 6.3 Hz, 2H), 2.82 (t, J = 7.5 Hz, 2H), 2.05 - 1.94 (m, 4H), 1.81 - 1.74 (m, 2H), 1.29 (t, J = 7.1 Hz, 2H), 0.97 (s, 9H), 0.13 (s, 6H). 13 13C NMR (100 MHz, CDCl3) δ 171.27, 158.45, 156.60, 154.95, 145.40, 142.93, 136.66, 135.52, 134.14, 130.14, 128.70, 128.37, 128.28, 127.85, 126.74, 120.93, 117.18, 113.13, 108.73, 85.93, 67.00, 65.53, 63.00, 60.51, 55.32, 53.55, 41.19, 38.74, 30.51, 29.85, 27.33, 26.14, 24.78, 21.17, 18.57, 14.33. (4) Preparation of Compound A96

[0403]

Chem.

[0404] To a solution of compound A94 (264 mg, 0.319 mmol, 1.0 eq) in MeOH (5 mL), Pd / C (16 mg) was slowly added under a nitrogen atmosphere. Next, the reaction atmosphere was replaced with hydrogen three times. Then, the reaction mixture was purged with a hydrogen balloon and stirred at room temperature overnight. Subsequently, the reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (8 mL), and then compound A77 (74 mg, 0.38 mmol, 1.2 eq), HBTU (242 mg, 0.64 mmol, 2.0 eq) and DIPEA (179 μL, 1.08 mmol, 3.4 eq) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Then, H2O (10 mL) was added to the reaction, and the mixture was extracted three times with DCM (3 * 10 mL). The organic phases were combined, dried over Na2SO4 and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A96 (236 mg, 85% yield) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 869.52; MW.Found: 303.2 [DMT] - , 568.4 [DMT off + H] + . 1 HNMR (400 MHz, CDCl3) δ 7.67 (s, 1H), 7.44 - 7.39 (m, 2H), 7.32 - 7.27 (m,5H), 7.26 - 7.14 (m, 4H), 6.83 - 6.78 (m, 4H), 4.83 (s, 2H),4.11 (t, J = 7.4 Hz, 2H), 3.78 (s, 6H), 3.25 (dd, J=13.2, 6.7 Hz, 2H), 3.10 (t, J = 6.2 Hz, 2H),2.86 (dd, J = 9.5, 5.9 Hz, 2H), 1.97 (d, J = 13.0 Hz, 6H), 1.85 (s, 2H), 1.74 - 1.65 (m,6H), 1.59 (dd, J = 13.7, 7.1 Hz, 9H), 0.94 (s, 9H), 0.10 (s, 6H). (5) Preparation of compound A97

[0405]

Chem.

[0406] To a solution of compound A96 (223 mg, 0.26 mmol, 1.0 eq) in anhydrous THF (7 mL) was added 1M TBAF THF solution (1.54 mL, 1.54 mmol, 6.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (10 mL), and DMAP (110 mg, 0.90 mmol, 3.5 eq) and succinic anhydride (52 mg, 0.52 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, and the mixture was extracted with DCM (3 × 10 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to obtain compound A97 (116 mg, 53% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 855.45; MW.Found: 303.2 [DMT] - , 554.3 [DMT off + H] + . 1HNMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.42 (dd, J = 7.0, 1.5 Hz, 2H), 7.37 (s,1H), 7.32 - 7.26 (m, 6H), 7.18 (t, J = 7.2 Hz, 2H), 6.82 - 6.79 (m, 4H), 5.19 (s, 2H),4.28 - 4.12 (m, 2H), 3.78 (s,6H), 3.24 (s, 2H), 3.09 (t,J = 6.2 Hz, 2H), 2.88 - 2.83 (m, 2H), 2.64 (t, J = 3.9 Hz, 4H), 1.96 (d,J = 13.0 Hz, 6H), 1.84 (s, 2H), 1.73 - 1.66 (m, 6H), 1.57 (dd, J =13.7, 7.1 Hz, 9H). (6) Preparation of Compound A6

[0407] [Chemical formula]

[0408] To a solution of compound A97 (100 mg, 0.117 mmol, 1.0 eq), controlled pore glass (CPG) (2.05 g), and DIPEA (58 μL, 0.35 mmol, 3.0 eq) in acetonitrile (14 mL) was added HBTU (89 mg, 0.234 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (7.02 mL), pyridine (13.5 mL), and NEt3 (211 μL) in acetonitrile (9 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce compound A16 (1.76 g) of the present disclosure.

[0409] Example 6: Preparation of Compound A7 of the Present Disclosure In this example, compound A7 was prepared according to the following procedure.

[0410] [Chemical formula]

[0411] (1) Preparation of Compound A99

[0412] [Chemical formula]

[0413] To a solution of methyl 2-(4-fluoro-3-nitrobenzoate) A69 (8.0 g, 40.2 mmol, 1.0 eq) and K2CO3 (5.5 g, 40.2 mmol, 1.0 eq) in anhydrous DMF (100 mL) under a nitrogen atmosphere, compound A98 (8.57 g, 40.2 mmol, 1.0 eq) was added. The reaction mixture was stirred at 25 °C for 6 hours, and then cold water (100 mL) was added. The mixture was extracted three times with ethyl acetate, and the organic phase was washed three times with a saturated lithium chloride solution and once with brine. Then, it was dried over anhydrous Na2SO4 and concentrated under reduced pressure to form a brown oil (compound A99). This oil was used directly in the next step without further purification.

[0414] (2) Preparation of Compound A100

[0415] [Chemical formula]

[0416] To a solution of compound A99 (15.76 g, 40.17 mmol, 1.0 eq) in THF / H2O (9:1, 165 mL) under an ice bath, HCOONH4 (15.21 g, 241 mmol, 6.0 eq) and Zn powder (15.76 g, 241 mmol, 6.0 eq) were added. After 10 minutes, the reaction mixture was transferred to room temperature and stirred overnight. Then, the reaction mixture was filtered and concentrated under reduced pressure. Thereafter, water (100 mL) was added to the mixture, and the mixture was extracted three times with ethyl acetate, and the organic phase was washed once with brine. After drying over anhydrous Na2SO4 and concentrating under reduced pressure, the resulting brown solid compound A100 was used directly in the next step without further purification. This compound was characterized by mass spectrometry. MW calc: 362.29; MW.Found: 363.4 [M+H] + . (3) Preparation of compound A102

[0417]

Chemical formula

[0418] To a solution of compound A100 (6.0 g, 16.56 mmol, 1.0 eq) in EtOH (100 mL), compound A91 (1.69 g, 16.56 mmol, 1.0 eq) and AcOH (3.8 mL, 66.24 mmol, 4.0 eq) were added. The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then saturated NaHCO3 solution (100 mL) was added, and the mixture was extracted three times with ethyl acetate. Then the organic phases were combined, washed with brine, dried over Na2SO4 and concentrated. The resulting residue compound was used directly in the next step without further purification. This compound was characterized by mass spectrometry. MW calc: 444.34; MW.Found: 445.4 [M+H] + . The obtained residue (1.0 g, 2.25 mmol, 1.0 eq) was dissolved in 10 mL of DCM, and Et3N (0.47 mL, 3.37 mmol, 1.5 eq) and DMTrCl (915 mg, 2.7 mmol, 1.2 eq) were added. After stirring the reaction mixture at room temperature for 6 hours, it was concentrated under reduced pressure. The obtained residue compound was used directly in the next step without further purification. This product A102 was characterized by mass spectrometry. MW calc: 746.47; MW.Found: 303.2 [DMT] - . (4) Preparation of Compound A103

[0419]

Chemical formula

[0420] To a solution of compound A102 (1.6 g, 2.16 mmol, 1.0 eq) in anhydrous THF (13 mL), LiAlH4 (123 mg, 3.24 mmol, 1.5 eq) was added under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath, and saturated sodium potassium tartrate solution (10 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The crude product (500 mg, 0.70 mmol, 1.0 eq) was dissolved in DCM (10 mL), and DMAP (298 mg, 2.45 mmol, 3.5 eq) and succinic anhydride (140 mg, 1.40 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, the mixture was extracted with DCM (3×10 mL), the organic phases were combined, dried over Na2SO4, and concentrated. The obtained residue was purified by flash chromatography. The obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1-10% MeOH / DCM) to obtain compound A103 (285 mg, yield 53%) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 818.49; MW.Found: 303.2 [DMT] -, 517.4 [DMT off + H] + . 1 HNMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.41 (d, J = 7.6 Hz, 2H), 7.30 (d, J = 8.8 Hz, 5H), 7.25 - 7.15 (m, 4H), 6.80 (d, J = 8.8 Hz, 4H), 5.26 (s, 2H), 4.04 (d, J = 7.2 Hz, 2H), 3.77 (s, 6H), 3.11 (t, J = 6.1 Hz, 2H), 2.90 (t, J = 7.7 Hz, 2H), 2.69 (dd, J = 8.4, 4.5 Hz, 4H), 2.02 - 1.95 (m, 2H), 1.74 (dd, J = 13.4, 6.9 Hz, 4H), 1.28 - 1.24 (m, 22H), 0.87 (t, J = 6.7 Hz, 3H). (5) Preparation of Compound A7

[0421]

Chemical formula

[0422] To a solution of compound A103 (124 mg, 0.15 mmol, 1.0 eq), controlled pore glass (CPG) (2.66 g), and DIPEA (75 μL, 0.45 mmol, 3.0 eq) in acetonitrile (20 mL) was added HBTU (115 mg, 0.30 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (9.06 mL), pyridine (17.4 mL), and NEt3 (272 μL) in acetonitrile (11.6 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce compound A17 (2.4 g) of the present disclosure.

[0423] Example 7: Preparation of Compound A8 of the Present Disclosure In this example, compound A8 was prepared according to the following procedure.

[0424]

Chem.

[0425] (1) Preparation of Compound A105

[0426]

Chem.

[0427] To a solution of methyl 4-fluoro-3-nitrobenzoate A104 (15 g, 75.3 mmol, 1.0 eq) and K2CO3 (10.4 g, 75.3 mmol, 1.0 eq) in anhydrous DMF (240 mL), compound 69 (18.18 g, 75.3 mmol, 1.0 eq) was added under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C for 6 h, then cold water (100 mL) was added. The mixture was extracted three times with ethyl acetate, and the organic phase was washed three times with saturated lithium chloride solution and once with brine. It was then dried over anhydrous Na2SO4 and concentrated under reduced pressure to form a brown oil (compound A105). This oil was used directly in the next step without further purification.

[0428] (2) Preparation of Compound A106

[0429]

Chem.

[0430] To a solution of compound A105 (31.65 g, 75.3 mmol, 1.0 eq) in THF / H2O (9:1, 300 mL) under an ice bath, HCOONH4 (28.5 g, 451.8 mmol, 6.0 eq) and Zn powder (29.5 g, 451.8 mmol, 6.0 eq) were added. After 10 minutes, the reaction mixture was transferred to room temperature and stirred overnight. Then, the reaction mixture was filtered and concentrated under reduced pressure. Thereafter, water (100 mL) was added to the mixture, and the mixture was extracted three times with ethyl acetate, and the organic phase was washed once with brine. After drying over anhydrous Na2SO4 and concentrating under reduced pressure, the resulting brown solid compound A106 was used directly in the next step without further purification.

[0431] (3) Preparation of compound A107

[0432]

Chemical formula

[0433] To a solution of compound A106 (6.0 g, 15.4 mmol, 1.0 eq) in EtOH (90 mL), compound A101 (1.57 g, 15.4 mmol, 1.0 eq) and AcOH (3.5 mL, 61.6 mmol, 4.0 eq) were added. The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then, saturated NaHCO3 solution (80 mL) was added, and the mixture was extracted three times with ethyl acetate. Then, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue was used directly in the next step without further purification. The resulting residue was characterized by mass spectrometry. MW calc: 472.37; MW.Found: 473.4 [M+H] + . The obtained residue (1.0 g, 2.12 mmol, 1.0 eq) was dissolved in 10 mL of DCM, and Et3N (0.44 mL, 3.17 mmol, 1.5 eq) and DMTrCl (860 mg, 2.54 mmol, 1.2 eq) were added. After the reaction mixture was stirred at room temperature for 6 hours, it was concentrated under reduced pressure. The obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A106 (1.27 g, yield 77%) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 774.50; MW.Found: 303.2 [DMT] - , 473.4 [DMT off + H] + . 1 HNMR (400 MHz, CDCl3) δ 8.42 (d, J = 0.9 Hz, 1H), 7.97 (dd, J = 8.5, 1.4 Hz, 1H), 7.42 (d, J = 7.4 Hz, 2H), 7.33 - 7.28 (m, 5H), 7.25 (d, J= 6.8 Hz, 2H), 7.19 (t, J = 7.3 Hz, 1H),6.80 (dd, J = 9.4, 2.4 Hz, 4H), 4.05 (t, J = 7.5 Hz, 2H), 3.93 (s, 3H), 3.78 (s, 6H),3.12 (t, J = 6.3 Hz, 2H), 2.92 - 2.80 (m, 2H), 2.07 - 1.97 (m,2H), 1.82 - 1.71 (m, 4H), 1.28 - 1.24 (m, 26H), 0.88 (t, J= 6.8 Hz, 3H). (4) Preparation of Compound A108

[0434]

Chemical Structure

[0435] To a solution of compound A107 (1.27 g, 1.64 mmol, 1.0 eq) in anhydrous THF (10 mL) was added LiAlH4 (93 mg, 2.46 mmol, 1.5 eq) under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath and saturated sodium potassium tartrate solution (10 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The crude product (500 mg, 0.67 mmol, 1.0 eq) was dissolved in DCM (10 mL), and DMAP (286 mg, 2.34 mmol, 3.5 eq) and succinic anhydride (134 mg, 1.34 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, the mixture was extracted with DCM (3 × 10 mL), the organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to give compound A108 (425 mg, 62% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 846.52; MW.Found: 303.2 [DMT] - , 545.4 [DMT off + H] + . 1HNMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.42 (d, J = 7.5 Hz, 2H), 7.30 (d, J = 8.8 Hz, 4H), 7.25 (d, J = 7.6 Hz, 3H), 7.19 (dd, J = 14.9, 7.9 Hz, 2H), 6.80 (d, J = 8.8 Hz, 4H), 5.26 (s, 2H), 4.03 (t, J = 7.4 Hz, 2H), 3.77 (s, 6H), 3.11 (t, J = 6.1 Hz, 2H), 2.90 (t, J = 7.7 Hz, 2H), 2.73 - 2.66 (m, 4H), 1.99 (dt, J = 15.3, 7.7 Hz, 2H), 1.74 (dd, J = 13.5, 6.9 Hz, 4H), 1.29 - 1.25 (m, 26H), 0.87 (t, J = 6.7 Hz, 3H). (5) Preparation of Compound A8

[0436] [Chemical formula]

[0437] To a solution of Compound A108 (114 mg, 0.134 mmol, 1.0 eq), controlled pore glass (CPG) (2.36 g), and DIPEA (67 μL, 0.4 mmol, 3.0 eq) in acetonitrile (18 mL) was added HBTU (102 mg, 0.268 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (8.04 mL), pyridine (15.5 mL), and NEt3 (241 μL) in acetonitrile (10 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce Compound A18 (2.2 g) of the present disclosure.

[0438] Example 8: Preparation of Compound A9 of the Present Disclosure In this example, Compound A9 was prepared by the following procedure.

[0439]

Chem.

[0440] (1) Preparation of Compound A110

[0441]

Chem.

[0442] To a solution of methyl 2-(4-fluoro-3-nitrobenzoate) A69 (8.0 g, 40.2 mmol, 1.0 eq) and K2CO3 (5.55 g, 40.2 mmol, 1.0 eq) in anhydrous DMF (128 mL), under a nitrogen atmosphere, compound A109 (10.83 g, 40.2 mmol, 1.0 eq) was added. The reaction mixture was stirred at 25 °C for 6 hours, then cold water (100 mL) was added. The mixture was extracted three times with ethyl acetate, and the organic phase was washed three times with saturated lithium chloride solution and once with brine. Then, it was dried over anhydrous Na2SO4 and concentrated under reduced pressure to form a brown oil (compound A110). This oil was used directly in the next step without further purification.

[0443] (2) Preparation of Compound A111

[0444]

Chem.

[0445] A solution of compound A110 (13 g, 29 mmol, 1.0 eq) in THF / H2O (9:1, 120 mL) was added with HCOONH4 (10.98 g, 174 mmol, 6.0 eq) and Zn powder (11.38 g, 174 mmol, 6.0 eq) under an ice bath. After 10 minutes, the reaction mixture was transferred to room temperature and stirred overnight. Then, the reaction mixture was filtered and concentrated under reduced pressure. Thereafter, water (100 mL) was added to the mixture, and the mixture was extracted three times with ethyl acetate, and the organic phase was washed once with brine. After drying over anhydrous Na2SO4 and concentrating under reduced pressure, the product 111 was used directly in the next step without further purification.

[0446] (3) Preparation of compound A112

[0447] [Chemical formula]

[0448] To a solution of compound A111 (6.0 g, 14.34 mmol, 1.0 eq) in EtOH (80 mL) were added compound A101 (1.46 g, 14.34 mmol, 1.0 eq) and AcOH (3.3 mL, 57.36 mmol, 4.0 eq). The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then saturated NaHCO3 solution (80 mL) was added, and the mixture was extracted three times with ethyl acetate. Then the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The obtained residue was used directly in the next step without further purification. The obtained residue was characterized by mass spectrometry. MW calc: 500.40; MW.Found: 501.4 [M+H] + . The obtained residue (1.5 g, 3.0 mmol, 1.0 eq) was dissolved in 10 mL of DCM, and Et3N (0.44 mL, 4.5 mmol, 1.5 eq) and DMTrCl (1.2 g, 3.6 mmol, 1.2 eq) were added. After the reaction mixture was stirred at room temperature for 6 hours, it was concentrated under reduced pressure. The obtained residue compound was used directly in the next step without further purification. This product A112 was characterized by mass spectrometry. MW calc: 802.53; MW.Found: 303.2 [DMT]- . (4) Preparation of Compound A113

[0449]

Chem.

[0450] To a solution of Compound A112 (1.7 g, 2.12 mmol, 1.0 eq) in anhydrous THF (15 mL), LiAlH4 (121 mg, 3.18 mmol, 1.5 eq) was added under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath, and saturated sodium potassium tartrate solution (10 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The crude product (500 mg, 0.65 mmol, 1.0 eq) was dissolved in DCM (10 mL), and DMAP (276 mg, 2.27 mmol, 3.5 eq) and succinic anhydride (129 mg, 1.29 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, the mixture was extracted with DCM (3 × 10 mL), the organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to obtain Compound A113 (340 mg, 60% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 874.55; MW.Found: 303.2 [DMT] - , 573.4 [DMT off + H] + . 11H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.42 (d, J = 7.5 Hz, 2H), 7.30 (d, J = 8.8 Hz, 4H), 7.26 - 7.22 (m, 4H), 7.17 (d, J = 8.0 Hz, 1H), 6.81 (t, J = 5.8 Hz, 4H), 5.26 (s, 2H), 4.02 (t, J = 7.4 Hz, 2H), 3.77 (s, 6H), 3.11 (t, J = 6.1 Hz, 2H), 2.88 (t, J = 7.7 Hz, 2H), 2.69 (dt, J = 10.5, 5.3 Hz, 4H), 1.97 (dd, J = 15.0, 7.6 Hz, 2H), 1.74 (dd, J = 13.5, 6.9 Hz, 4H), 1.28 - 1.25 (m, 30H), 0.87 (t, J = 6.8 Hz, 3H). (5) Preparation of Compound A9

[0451] [Chemical formula]

[0452] To a solution of Compound A113 (100 mg, 0.114 mmol, 1.0 eq), controlled pore glass (CPG) (2.0 g), and DIPEA (57 μL, 0.342 mmol, 3.0 eq) in acetonitrile (15 mL) was added HBTU (86 mg, 0.228 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (6.8 mL), pyridine (13 mL), and NEt3 (210 μL) in acetonitrile (9 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce Compound A19 (1.87 g) of the present disclosure.

[0453] Example 9: Preparation of Compound A13 and Compound A13 of the Present Disclosure In this example, Compounds A10 and A13 were prepared using the following procedure.

[0454]

Chem.

[0455] (1) Preparation of Compound A115

[0456]

Chem.

[0457] To a solution of Compound A106 (2.0 g, 5.12 mmol, 1.0 eq) in EtOH (30 mL) were added Compound A114 (790 mg, 5.12 mmol, 1.0 eq) and AcOH (1.18 mL, 20.48 mmol, 4.0 eq). The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then saturated NaHCO3 solution (20 mL) was added, and the mixture was extracted three times with ethyl acetate. Then the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 25% EA / hexane) to give Compound A115 (1.46 g, 54% yield) as a yellow oil. This product was characterized by mass spectrometry. MW calc: 524.43; MW Found: 525.5 [M+H] + . (2) Preparation of Compound A116

[0458]

Chem.

[0459] To a solution of compound A115 (500 mg, 0.95 mmol, 1.0 eq) in MeOH (18 mL) was added 18 mL of 0.5 M aqueous NaOH. The mixture was stirred overnight. The reaction was then acidified with 2 M HCl, and the mixture was extracted three times with Et2O. The combined organic phases were washed with brine, dried over Na2SO4, and concentrated. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to afford the compound A116 of the present disclosure (400 mg, 82% yield) as a white solid. This product was characterized by mass spectrometry. MW calc: 510.42; MW Found: 511.4 [M + H] + . (3) Preparation of Compound A117

[0460]

Chemical Structure

[0461] To a solution of compound A94 (298 mg, 0.36 mmol, 1.0 eq) in MeOH (5 mL), Pd / C (30 mg) was slowly added under a nitrogen atmosphere. Next, the reaction atmosphere was replaced with hydrogen three times. Then, the reaction mixture was purged with a hydrogen balloon and stirred at room temperature overnight. Subsequently, the reaction mixture was filtered and concentrated under reduced pressure to obtain crude product A95. The crude product A95 was dissolved in DCM (5 mL), and then compound A116 (220 mg, 0.432 mmol, 1.2 eq), HBTU (273 mg, 0.72 mmol, 2.0 eq), and DIPEA (179 μL, 1.224 mmol, 3.4 eq) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Then, H2O (10 mL) was added to the reaction, and the mixture was extracted three times with DCM (3 * 10 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A117 (400 mg, 94% yield) as a yellow oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 1185.80; MW.Found: 303.2 [DMT] - . 11H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 1.3 Hz, 1H), 7.43 - 7.40 (m, 2H), 7.32 - 7.26 (m, 8H), 7.23 (dd, J = 11.0, 4.3 Hz, 3H), 7.18 (dd, J = 7.9, 1.8 Hz, 1H), 6.81 - 6.78 (m, 4H), 6.38 (t, J = 5.8 Hz, 1H), 5.09 (t, J = 7.0 Hz, 1H), 4.83 (s, 2H), 4.18 (t, J = 7.3 Hz, 2H), 4.11 - 4.07 (m, 2H), 3.76 (s, 6H), 3.49 (dd, J = 13.0, 6.6 Hz, 2H), 3.09 (t, J = 6.2 Hz, 2H), 2.91 - 2.83 (m, 4H), 2.14 - 2.01 (m, 5H), 1.80 - 1.73 (m, 4H), 1.67 (s, 3H), 1.59 (s, 3H), 1.32 - 1.25 (m, 30H), 0.99 (d, J = 6.6 Hz, 3H), 0.94 (s, 9H), 0.87 (d, J = 4.6 Hz, 3H), 0.10 (s, 6H). (4) Preparation of Compound A118

[0462] [Chemical formula]

[0463] To a solution of compound A117 (400 mg, 0.337 mmol, 1.0 eq) in anhydrous THF (8 mL) was added 1M TBAF THF solution (2.02 mL, 2.02 mmol, 6.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (10 mL), and DMAP (144 mg, 1.18 mmol, 3.5 eq) and succinic anhydride (67 mg, 0.674 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, and the mixture was extracted with DCM (3 × 20 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to obtain compound A118 (235 mg, 60% yield) as a white solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 1171.73; MW Found: 303.2 [DMT] - , 871.3 [DMT off + H] + . 11H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.65 (s, 1H), 7.41 (d, J = 7.6 Hz, 2H), 7.31 - 7.24 (m, 9H), 7.18 (dd, J = 7.9, 5.6 Hz, 2H), 6.80 (d, J = 8.8 Hz, 4H), 5.20 (s, 2H), 5.07 (d, J = 6.3 Hz, 1H), 4.13 (dt, J = 15.1, 7.1 Hz, 4H), 3.76 (s, 6H), 3.33 (dd, J = 11.3, 5.6 Hz, 4H), 3.09 (t, J = 6.2 Hz, 2H), 2.83 (t, J = 7.6 Hz, 2H), 2.72 - 2.68 (m, 4H), 2.15 - 2.04 (m, 5H), 1.76 (dd, J = 15.1, 7.9 Hz, 4H), 1.67 (s, 3H), 1.60 (s, 3H), 1.31 - 1.26 (m, 30H), 0.96 (s, 3H), 0.87 (d, J = 7.0 Hz, 3H). (5) Preparation of Compound A10

[0464] [Chemical formula]

[0465] To a solution of Compound A118 (170 mg, 0.145 mmol, 1.0 eq) in acetonitrile (15 mL), controlled pore glass (CPG) (2.54 g), and DIPEA (72 μL, 0.435 mmol, 3.0 eq) under a nitrogen atmosphere, HBTU (110 mg, 0.29 mmol, 2.0 eq) was added. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. To a solution of acetic anhydride (8.67 mL), pyridine (16.8 mL), and NEt3 (260 μL) in acetonitrile (11 mL) under a nitrogen atmosphere, the crude solid support was added. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce the compound A10 (2.38 g) of the present disclosure.

[0466] (6) Preparation of Compound A13

[0467] [Chemical formula]

[0468] To a solution of compound A116 (400 mg, 0.76 mmol, 1.0 eq) in anhydrous THF (5 mL) was added LiAlH4 (43 mg, 1.14 mmol, 1.5 eq) under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath and saturated sodium potassium tartrate solution (10 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated to give a crude composition. To a solution of the crude compound and DIPEA (378 μL, 2.28 mmol, 3.0 eq) in anhydrous DCM (5 mL) was added 3-((chloro(diisopropylamino)phosphanyl)oxy)propanenitrile (540 mg, 2.28 mmol, 3.0 eq) at 25 °C under a nitrogen atmosphere. The reaction mixture was stirred for 1 hour. The mixture was extracted twice with DCM, then washed with brine and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM, 1% Et3N) to give compound A13 (397 mg, 75% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 696.55; MW Found: 614.4 [M - diisopropylamine + 2H] + . 1HNMR (400 MHz, CDCl3) δ 7.68 (s, 1H), 7.25 (dd, J = 8.6, 3.9 Hz, 2H), 4.85 (dd, J = 11.9, 8.3 Hz, 1H), 4.75 (dd, J = 11.9, 9.0 Hz, 1H), 4.10 - 4.04 (m, 2H), 3.90 - 3.78 (m,2H), 3.73 - 3.60 (m, 2H), 2.73 (d, J = 7.2 Hz, 2H), 2.61 (td, J = 6.5, 1.4 Hz, 2H), 1.98 - 1.92 (m, 1H), 1.88 - 1.52 (m,8H), 1.36 - 1.23 (m, 31H), 1.21 (dd, J = 6.8, 0.7 Hz, 12H), 1.15 - 0.98 (m, 3H), 0.88 (t, J= 6.8 Hz, 3H). Example 10: Preparation of Compound A11 and Compound A15 of the Present Disclosure In this example, compounds A11 and A15 were prepared using the following procedure.

[0469] [ka]

[0470] (1) Preparation of Compound A120

[0471] [ka]

[0472] To a solution of compound A106 (2.0 g, 5.12 mmol, 1.0 eq) in EtOH (30 mL), compound A119 (958 mg, 5.12 mmol, 1.0 eq) and AcOH (1.18 mL, 20.48 mmol, 4.0 eq) were added. The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then saturated NaHCO3 solution (30 mL) was added, the mixture was extracted three times with ethyl acetate, then the organic phases were combined, washed with brine, dried over Na2SO4 and concentrated. The resulting residue compound A120 was used directly in the next step without further purification. This compound A120 was characterized by mass spectrometry. MW calc: 557.36; MW.Found: 558.4 [M + H] + . (2) Preparation of compound A122

[0473]

Chemical formula

[0474] To a solution of compound A121 (500 mg, 0.9 mmol, 1.0 eq) in MeOH (18 mL), 18 mL of 0.5 M aqueous NaOH was added. The mixture was stirred overnight. Then the reaction was acidified with 2 M HCl, the mixture was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4 and concentrated. The organic layer was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to give the compound A122 of the present disclosure (330 mg, 68% yield) as a white solid. This product was characterized by mass spectrometry. MW calc: 543.35; MW.Found: 544.5 [M + H] + . (3) Preparation of compound A123

[0475]

Chemical formula

[0476] To a solution of compound A94 (273 mg, 0.33 mmol, 1.0 eq) in MeOH (5 mL), Pd / C (27 mg) was slowly added under a nitrogen atmosphere. Next, the reaction atmosphere was replaced with hydrogen three times. Then, the reaction mixture was purged with a hydrogen balloon and stirred at room temperature overnight. Subsequently, the reaction mixture was filtered and concentrated under reduced pressure to obtain the crude product A95. The crude product A95 was dissolved in DCM (5 mL), and then compound A122 (229 mg, 0.33 mmol, 1.2 eq), HBTU (250 mg, 0.66 mmol, 2.0 eq) and DIPEA (179 μL, 1.12 mmol, 3.4 eq) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Then, H2O (5 mL) was added to the reaction, and the mixture was extracted three times with DCM (3 * 10 mL). The organic phases were combined, dried over Na2SO4 and concentrated. The residue obtained was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain compound A123 (249 mg, 62% yield) as a white solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 1218.73; MW Found: 303.2 [DMT] - . 11H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 8.28 (s, 1H), 7.73 - 7.69 (m, 2H), 7.56 (s, 1H), 7.29 (d, J = 7.0 Hz, 3H), 7.18 - 7.15 (m, 6H), 7.07 (dt, J = 9.2, 8.5 Hz, 6H), 6.67 (d, J = 8.9 Hz, 4H), 4.72 (s, 2H), 4.12 - 4.05 (m, 2H), 3.96 (t, J = 7.0 Hz, 2H), 3.64 (s, 6H), 3.12 (d, J = 6.4 Hz, 2H), 2.95 (t, J = 6.3 Hz, 2H), 2.70 - 2.63 (m, 7H), 1.82 (dd, J = 17.3, 10.5 Hz, 4H), 1.59 (dd, J = 12.8, 6.9 Hz, 4H), 1.18 - 1.04 (m, 24H), 0.83 (s, 9H), 0.75 (d, J = 7.0 Hz, 3H), 0.03 (s, 6H). (4) Preparation of Compound A124

[0477] [Chemical formula]

[0478] To a solution of compound A123 (230 mg, 0.19 mmol, 1.0 eq) in anhydrous THF (5 mL) was added 1M TBAF THF solution (1.13 mL, 1.13 mmol, 6.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (6 mL), and DMAP (81 mg, 0.66 mmol, 3.5 eq) and succinic anhydride (38 mg, 0.38 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, and the mixture was extracted with DCM (3 × 10 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to obtain compound A124 (126 mg, 55% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 1204.66; MW Found: 303.2 [DMT] - . 1 H NMR (400 MHz, CDCl3) δ 8.55(s, 1H), 8.07 (d, J =8.2 Hz, 2H), 7.73 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 10.8 Hz, 2H), 7.38 (d,J = 11.5 Hz, 4H), 7.28 (t, J = 8.1 Hz, 6H), 7.16 (t, J = 6.8 Hz, 4H), 6.79 (d,J = 8.7 Hz, 4H), 5.16 (s, 2H), 4.30 - 4.20 (m, 4H), 3.75 (s, 6H),3.58 (d, J = 5.1 Hz, 2H), 3.43 - 3.41 (m, 7H), 3.07 (s, 2H),2.86 (t, J = 7.2 Hz, 2H), 2.61 (d, J = 3.4 Hz, 4H), 2.21 - 2.15 (m, 2H), 1.98 - 1.93 (m,2H), 1.27 - 1.20 (m, 26H), 0.86 (d, J = 7.0 Hz, 3H). (5) Preparation of Compound A11

[0479]

Chem.

[0480] To a solution of compound A124 (126 mg, 0.104 mmol, 1.0 eq) in acetonitrile (12 mL), controlled pore glass (CPG) (1.83 g), and DIPEA (52 μL, 0.312 mmol, 3.0 eq) was added HBTU (79 mg, 0.208 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (6.2 mL), pyridine (12 mL), and NEt3 (186 μL) in acetonitrile (7.9 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce compound A11 (1.7 g) of the present disclosure.

[0481] (6) Preparation of Compound A15

[0482]

Chem.

[0483] To a solution of compound A121 (300 mg, 0.538 mmol, 1.0 eq.) in anhydrous THF (5 mL) was added LiAlH4 (31 mg, 0.8 mmol, 1.5 eq.) under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath and saturated sodium potassium tartrate solution (5 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated to produce a crude composition. To a solution of the crude compound and DIPEA (265 μL, 1.6 mmol, 3.0 eq) in anhydrous DCM (5 mL) was added 3-((chloro (diisopropylamino)phosphanyl)oxy)propanenitrile (379 mg, 1.6 mmol, 3.0 eq) at 25 °C under a nitrogen atmosphere. The reaction mixture was stirred for 1 hour. The mixture was extracted twice with DCM, then washed with brine and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM, 1% Et3N) to give compound A15 (274 mg, 70% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 729.47; MW Found: 669.5 [M -diisopropylamine + Na] + . 1 HNMR (400 MHz, CDCl3) δ 8.28 (s, 1H), 7.73 - 7.68 (m, 2H), 7.56 (s, 1H),7.18 - 7.15 (m, 4H), 4.72 (s,2H), 4.12 - 4.05 (m, 4H), 2.70 - 2.63 (m, 7H), 1.92 - 1.88(m,2H), 1.27 - 1.23 (m, 26H), 1.21 (dd, J = 6.8, 0.7 Hz, 12H), 0.88 (t, J = 6.8 Hz, 3H). Example 11: Preparation of Compound A12 of the Present Disclosure In this example, compound A12 was prepared by the following procedure.

[0484]

Chemical Structure

[0485] (1) Preparation of Compound A126

[0486] [Chem.]

[0487] To a solution of Compound A94 (298 mg, 0.36 mmol, 1.0 eq) in MeOH (5 mL), Pd / C (30 mg) was slowly added under a nitrogen atmosphere. Next, the reaction atmosphere was replaced with hydrogen three times. Then, the reaction mixture was purged with a hydrogen balloon and stirred at room temperature overnight. Subsequently, the reaction mixture was filtered and concentrated under reduced pressure to obtain crude product A95. The crude product A95 was dissolved in DCM (5 mL), and then Compound A125 (111 mg, 0.43 mmol, 1.2 eq), HBTU (273 mg, 0.72 mmol, 2.0 eq), and DIPEA (179 μL, 1.22 mmol, 3.4 eq) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Then, H2O (5 mL) was added to the reaction, and the mixture was extracted three times with DCM (3 * 10 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain Compound A126 (295 mg, yield 88%) as a yellow oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 931.63; MW Found: 303.2 [DMT] - . 11H NMR (400 MHz, CDCl3) δ 7.68 (s, 1H), 7.47 - 7.39 (m, 2H), 7.32 - 7.23 (m, 9H), 6.83 - 6.77 (m, 4H), 4.83 (s, 2H), 4.10 (t, J = 7.3 Hz, 2H), 3.78 (s, 6H), 3.24 (dd, J = 13.2, 6.7 Hz, 2H), 3.11 (t, J = 6.2 Hz, 2H), 2.06 (dd, J = 12.4, 4.5 Hz, 2H), 2.02 - 1.93 (m, 4H), 1.79 - 1.72 (m, 2H), 1.56 (d, J = 7.0 Hz, 2H), 1.29 - 1.23 (m, 26H), 0.94 (s, 9H), 0.87 (d, J = 7.0 Hz, 3H), 0.10 (s, 6H). (2) Preparation of Compound A127

[0488] [Chemical formula]

[0489] To a solution of compound A126 (270 mg, 0.29 mmol, 1.0 eq) in anhydrous THF (5 mL) was added 1M TBAF THF solution (1.74 mL, 1.74 mmol, 6.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in DCM (10 mL), and DMAP (124 mg, 1.02 mmol, 3.5 eq) and succinic anhydride (58 mg, 0.58 mmol, 2.0 eq) were added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then H2O (10 mL) was added to the reaction, and the mixture was extracted with DCM (3 × 10 mL). The organic phases were combined, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 10% MeOH / DCM) to obtain compound A127 (120 mg, 45% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 917.56; MW Found: 303.2 [DMT] - . 1 H NMR (400 MHz, CDCl3) δ7.64 (s, 1H), 7.46 - 7.40 (m,3H), 7.31 (d, J = 8.8 Hz, 4H), 7.25 (d, J = 7.8 Hz, 2H), 7.20 (t, J = 7.7 Hz, 2H), 6.80 (d, J = 8.8 Hz, 4H), 5.18 (s, 2H), 4.31 - 4.18 (m,2H), 3.78 (s, 6H), 3.42 - 3.40 (m, 4H), 3.09 (t, J=6.3 Hz, 2H), 2.87 (t, J = 7.5 Hz, 2H), 2.67- 2.62 (m, 4H), 2.34 (t,J = 7.6 Hz, 2H), 2.05 - 1.92 (m, 4H), 1.29 -1.23 (m, 26H), 0.88 (t,J = 6.8 Hz, 3H). (3) Preparation of compound A12

[0490]

Chemical Structure

[0491] To a solution of Compound A127 (120 mg, 0.13 mmol, 1.0 eq), controlled pore glass (CPG) (2.29 g), and DIPEA (57 μL, 0.39 mmol, 3.0 eq) in acetonitrile (15 mL) was added HBTU (99 mg, 0.26 mmol, 2.0 eq) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce a crude solid support. The crude solid support was added to a solution of acetic anhydride (7.8 mL), pyridine (15 mL), and NEt3 (234 μL) in acetonitrile (10 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 25 °C overnight and then washed with DCM and ethyl ether to produce Compound A12 (2.1 g) of the present disclosure.

[0492] Example 12: Preparation of Compound A14 of the Present Disclosure In this example, Compound A14 was prepared by the following procedure.

[0493]

Chemical formula

[0494] (1) Preparation of Compound A129

[0495]

Chemical formula

[0496] To a solution of compound A106 (1.55 g, 3.96 mmol, 1.0 eq) in EtOH (20 mL), compound A128 (500 mg, 3.96 mmol, 1.0 eq) and AcOH (913 μL, 15.84 mmol, 4.0 eq) were added. The reaction mixture was stirred at 80 °C overnight and then concentrated under reduced pressure. Then saturated NaHCO3 solution (20 mL) was added, the mixture was extracted three times with ethyl acetate, then the organic phases were combined, washed with brine, dried over Na2SO4 and concentrated. The resulting residue, compound A129, was used directly in the next step without further purification. This compound A129 was characterized by mass spectrometry. MW calc: 496.40; MW.Found: 497.5 [M+H] + . (2) Preparation of compound A14

[0497]

Chemical formula

[0498] To a solution of compound A129 (400 mg, 0.806 mmol, 1.0 eq) in anhydrous THF (5 mL) was added LiAlH4 (46 mg, 1.2 mmol, 1.5 eq) under a nitrogen atmosphere and an ice bath. The mixture was transferred to room temperature after 10 minutes and stirred for 1 hour. Next, the reaction was transferred to an ice bath and saturated sodium potassium tartrate solution (5 mL) was slowly added. After 30 minutes, the reaction was extracted three times with Et2O, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated to give a crude composition. To a solution of the crude compound and DIPEA (401 μL, 2.42 mmol, 3.0 eq) in anhydrous DCM (5 mL) was added 3-((chloro(diisopropylamino)phosphanyl)oxy)propanenitrile (573 mg, 2.42 mmol, 3.0 eq) at 25 °C under a nitrogen atmosphere. The reaction mixture was stirred for 1 hour. The mixture was extracted twice with DCM, then washed with brine and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 3% MeOH / DCM, 1% Et3N) to give compound A14 (339 mg, 63% yield) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. MW calc: 668.52; MW Found: 607.4 [M - diisopropylamine + Na] + . 11H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.19 (dd, J = 6.9, 2.8 Hz, 2H), 5.03 (t, J = 7.0 Hz, 1H), 4.81 - 4.79 (m, 1H), 4.71 - 4.66 (m,1H), 4.04 - 3.98 (m, 2H), 3.79 (dd, J = 6.9, 2.8 Hz, 1H), 3.60 (ddd, J = 13.6, 6.8, 3.4 Hz, 2H), 2.82 - 2.78 (m, 1H), 2.61 - 2.53 (m,3H), 1.63 - 1.60 (m, 3H), 1.54 - 1.52 (m, 3H), 1.33 - 1.17 (m,30H), 1.14 (dd, J = 6.8, 2.0 Hz, 12H), 0.92 (d, J = 6.6 Hz, 3H), 0.82 (t, J = 6.8 Hz, 3H). Example 13: Preparation of Compound B1 of the Present Disclosure In this example, Compound B1 was prepared according to the following procedure.

[0499]

Chemical Structure

[0500] Compound B1 (1) Preparation of Compound B12 from 4-Fluoro-3-nitrobenzoic Acid

[0501]

Chemical Structure

[0502] To a solution of 4-fluoro-3-nitrobenzoic acid (35 g, 189.1 mmol, 1.0 eq) and K2CO3 (30.6 g, 283.6 mmol, 1.5 eq) in anhydrous DMF (500 mL), benzyl bromide (35.6 g, 207.98 mmol, 1.1 eq) was slowly added under a nitrogen atmosphere. The reaction mixture was stirred at 45 °C for 3 hours, and then cold water (200 mL) was added thereto. The mixture was extracted three times with ethyl acetate, and the organic phase was washed three times with a saturated lithium chloride solution and once with brine. The organic phase was then dried over anhydrous Na2SO4 and concentrated under reduced pressure to form a yellow oil (Compound B12). This oil was used directly in the next step without further purification.

[0503] (2) Preparation of Compound B13 from Compound B12 by an SNAr reaction of tert-butyl (3-aminopropyl)carbamate

[0504]

Chemical formula

[0505] To a solution of Compound B12 (52 g, 189.1 mmol, 1.0 eq) and K2CO3 (26.13 g, 189.1 mmol, 1.0 eq) in anhydrous DMF (500 mL), tert-butyl (3-aminopropyl)carbamate (32.9 g, 189.1 mmol, 1.0 eq) was added under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 3 hours, and then cold water (200 mL) was added. The mixture was extracted three times with ethyl acetate, and the organic phase was washed three times with a saturated lithium chloride solution and once with brine. After drying over anhydrous Na2SO4 and concentrating under reduced pressure, the resulting yellow solid B13 was used directly in the next step without further purification.

[0506] (3) Compound B14 was produced by the reduction of Compound B13.

[0507]

Chemical formula

[0508] To a solution of Compound B13 (81.16 g, 189.1 mmol, 1.0 eq) in THF / H2O (9:1, 600 mL) was added HCOONH4 (71.58 g, 1.134 mol, 6.0 eq) and Zn powder (74.19 g, 1.134 mol, 6.0 eq) under an ice bath. After 10 minutes, the reaction mixture was transferred to room temperature and stirred overnight. Then, the reaction mixture was filtered and concentrated under reduced pressure. Thereafter, water (200 mL) was added to the mixture, and the mixture was extracted three times with ethyl acetate, and the organic phase was washed once with brine. The organic brine was dried over anhydrous Na4SO4 and concentrated under reduced pressure. The resulting pale red solid (Compound B14) was used directly in the next step without further purification.

[0509] (4) Compound B15 was produced by acylating Compound B14 with N2,N6-bis(tert-butoxycarbonyl)-L-lysine.

[0510] [Chemical formula]

[0511] To a solution of Compound B14 (16.8 g, 42 mmol, 1.0 eq) in DCM (300 mL) were added N2,N6-bis(tert-butoxycarbonyl)-L-lysine (21.82 g, 63 mmol, 1.5 eq), EDCI (12.08 g, 63 mmol, 1.5 eq) and DMAP (2.565 g, 21 mmol, 0.5 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Next, 200 mL of H2O was added to the reaction mixture, and the mixture was extracted with DCM (3 × 100 mL). The combined organic phases were dried over Na2SO4 and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 50% EA / hexane) to obtain Compound 15 (27.5 g, 90% yield) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 727.42; MW Found: 728.47 [M+H] + . 11H NMR (400 MHz, CDCl3) δ 7.88 (dd, J = 8.6, 1.9 Hz, 1H), 7.79 (s,1H), 7.35 (ddt, J = 9.8, 7.1, 5.5 Hz, 5H), 6.62 (d, J = 8.6 Hz, 1H), 5.29 (s,2H), 4.16 (s, 1H), 3.37 - 2.97 (m, 6H), 1.78 (d, J = 25.4Hz, 4H), 1.51 (s, 2H), 1.48 - 1.35 (m, 27H), 1.36 - 1.13 (m,2H). (5) Compound B16 containing a benzimidazole structure was prepared from compound B15.

[0512] [Chemical formula]

[0513] Compound B15 (20 g, 27.5 mmol, 1.0 eq) was added to AcOH (100 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 95 °C for 4 hours. Next, saturated NaHCO3 solution (100 mL) was added thereto, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated NaHCO3 solution (3 × 100 mL), dried over Na2SO4, and concentrated. The obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 50% EA / hexane) to obtain compound B16 (8.78 g, yield 45%) as a white solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 709.41; MW Found: 710.57 [M+H] + . 11H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 8.04 (dd, J = 8.5, 1.4 Hz, 1H), 7.46 (d, J = 7.0 Hz, 2H), 7.41 (s, 1H), 7.38 - 7.34 (m, 3H), 5.39 (s, 2H), 5.02 (dd, J = 15.8, 7.7 Hz, 1H), 3.20 - 3.10 (m, 6H), 2.08 - 1.96 (m, 4H), 1.57 - 1.48 (m, 4H), 1.41 (d, J = 8.6 Hz, 27H). (6) Compound B17 was prepared using (2S,3R,4R,5R,6R)-3-acetamido-6-(acetoxymethyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate as the starting material.

[0514] [Chemical formula]

[0515] To a solution of (2S, 3R, 4R, 5R, 6R)-3-acetamido-6-(acetoxymethyl)tetrahydro-2H-pyran-2, 4, 5-triyl triacetate (30 g, 77 mmol, 1.0 eq) in DCM (300 mL) was added TMSOTf (15.3 mL, 84.7 mmol, 1.1 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 6 hours. Then, a NaHCO3 solution (prepared by dissolving 21 g of NaHCO3 in 200 mL of water) was added under an ice bath, and the reaction was returned to room temperature. After stirring for 30 minutes, the mixture was extracted three times with DCM. Then, the organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 50% EA / hexane) to obtain compound B17 (19.8 g, yield 78%). This product was characterized by mass spectrometry and 1H NMR. MW calc: 329.11; MW Found: 330.33 [M+H] + . 11H NMR (400 MHz, CDCl3) δ 5.97 (d, J = 9.5 Hz, 1H), 5.39 (s,1H), 5.26 (dd, J = 11.4, 3.2 Hz, 1H), 4.53 (td, J = 11.4, 3.4 Hz, 1H), 4.43 (t, J = 6.5 Hz, 1H), 4.27 (s,1H), 4.11 - 4.08 (m, 1H), 2.17 (s, 3H), 2.05 (s, 3H),2.00 (d, J = 7.3 Hz, 6H). (7) The alkoxy group terminated with a vinyl group was bonded to Compound B17.

[0516] [Chemical formula]

[0517] To a solution of Compound B17 (15 g, 45.6 mmol, 1.0 eq) in DCE (200 mL) was added deca-9-en-1-ol (8.5 g, 54.7 mmol, 1.2 eq) and TMSOTf (1.6 mL, 9.1 mmol, 0.2 eq) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 6 hours. Then, saturated NaHCO3 solution (100 mL) was added, and the mixture was extracted 3 times with DCM. The organic phases were combined, washed with brine, dried over Na2SO4, and concentrated. The resulting residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 5% MeOH / DCM) to obtain Compound B20 (19.6 g, yield 89%). This product was characterized by mass spectrometry and 1H NMR. MW calc: 485.26; MW Found: 486.48 [M+H] + . 11H NMR (400 MHz, CDCl3) δ 5.84 - 5.74(m, 1H), 5.49 (d, J =8.5 Hz, 1H), 5.35 (d, J = 2.7 Hz, 1H), 5.33 - 5.25 (m, 2H), 5.01 - 4.88 (m,2H), 4.70 (d, J = 8.4 Hz, 1H), 4.20 - 4.07 (m, 2H), 3.94 - 3.80 (m,3H), 3.47 (dt, J = 9.5, 6.9 Hz, 1H), 2.13 (s, 3H), 2.03 (s, 3H),1.98 (d, J = 9.7 Hz, 3H), 1.95 (d, J = 10.1 Hz, 3H), 1.56 (d,J = 6.4 Hz, 2H), 1.35 (d, J = 6.7 Hz, 2H), 1.27 (s, 8H). (8) The terminal vinyl group of compound B20 was oxidized to a carboxyl group.

[0518]

Chemical formula

[0519] To a solution of compound B20 (19.6 g, 40.4 mmol, 1.0 eq) in ACN / DCM / H2O (50 mL / 50 mL / 60 mL) was added NaIO4 (34.6 g, 161.6 mol, 4.0 eq) and RuCl3·3H2O (1.66 g, 8.0 mol, 0.2 eq) under an ice bath. After 10 minutes, the reaction mixture was transferred to room temperature and stirred overnight. Then, the reaction mixture was filtered and concentrated under reduced pressure. Thereafter, water (50 mL) was added to the mixture, and the mixture was extracted 3 times with DCM. The organic phase was washed once with brine. After drying over anhydrous Na2SO4 and concentrating under reduced pressure, the obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 8% MeOH / DCM) to obtain compound B21 (17 g, yield 84%). This product was characterized by mass spectrometry and 1H NMR. MW calc: 503.24; MW Found: 504.49 [M+H] + . 11H NMR (400 MHz, CDCl3) δ 5.65 (d, J = 8.7 Hz, 1H), 5.35 (d, J = 2.8 Hz, 1H), 5.31 (d, J = 6.1 Hz, 1H), 4.68 (d, J = 8.3 Hz, 1H), 4.18 - 4.12 (m, 2H), 3.91 (dd, J = 11.8, 5.4 Hz, 2H), 3.48 (dd, J = 9.7, 6.7 Hz, 1H), 2.35 (t, J = 7.2 Hz, 2H), 2.15 (s, 3H), 2.05 (s, 3H), 2.01 (s, 3H), 1.96 (s, 3H), 1.63 (s, 2H), 1.32 (s, 10H). (9) Compounds B16 and B21 were combined.

[0520]

Chemical formula

[0521] To a solution of compound B16 (4.56 g, 6.4 mmol, 1.0 eq) in DCM (10 mL) was added HCl / dioxane (4 M, 30 mL). The reaction mixture was stirred at room temperature for 3 hours and then concentrated under reduced pressure to obtain the crude product as a yellow solid. The crude product was dissolved in DCM (50 mL), and then compound 21 (9.66 g, 19.2 mmol, 3.0 eq), HBTU (8.49 g, 3.4 mmol, 3.5 eq) and DIPEA (12.72 mL, 76.8 mmol, 12.0 eq) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. Next, 50 mL of H2O was added to the reaction mixture, and the mixture was extracted with DCM (3 × 50 mL). The organic phases were combined, dried over Na2SO4 and concentrated. The residue obtained was purified by flash chromatography (silica gel, gradient eluent: 1 - 8% MeOH / DCM) to obtain compound B22 (10.4 g, yield 87%) as a yellow solid. This product was characterized by mass spectrometry and 1H NMR. MW calc: 1864.93; MW Found: 1895.54 [M+H] + . 11H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 8.04 (dd, J =8.5, 1.4 Hz, 1H), 7.46 (d, J = 7.1 Hz, 2H), 7.36 (dd, J = 13.2, 7.3 Hz, 4H), 5.39 (s, 2H), 5.35 (d, J = 3.2Hz, 4H), 5.29 (s, 6H), 4.75 - 4.63 (m, 4H), 4.14 (qd, J =11.1, 6.8 Hz, 9H), 3.92 (dd, J = 13.0, 6.4 Hz, 6H),3.64 (dd, J = 13.0, 6.6 Hz, 4H), 3.49 - 3.42 (m, 4H), 3.12 - 3.06 (m,3H), 2.19 (dd, J = 11.6, 7.5 Hz, 6H), 2.13 (s, 9H), 2.03 (s, 9H),1.99 (s, 9H), 1.93 (d,J = 2.6 Hz, 9H), 1.54 - 1.50 (m, 12H), 1.45 (s, 6H), 1.25 (s, 18H). (10) Compound B22 was reduced to produce Compound B1 of the present disclosure.

[0522] [Chemical formula]

[0523] To a solution of Compound B22 (1.4 g, 0.75 mmol, 1.0 eq) in MeOH (25 mL), Pd / C (100 mg) was slowly added under a nitrogen atmosphere. Next, the reaction atmosphere was replaced three times with hydrogen gas. Then, the reaction mixture was purged with a hydrogen balloon and stirred at room temperature overnight. Subsequently, the reaction mixture was filtered, concentrated under reduced pressure, and the obtained residue was purified by flash chromatography (silica gel, gradient eluent: 1 - 15% MeOH / DCM) to obtain Compound B1 (1.2 g, yield 90%) as a colorless oil. This product was characterized by mass spectrometry and 1H NMR. This product was characterized by mass spectrometry an...

Claims

1. An oligonucleotide delivery enhancing compound comprising a nitrogen-containing five-membered heterocyclic moiety and at least one substituent capable of directly or indirectly binding to an oligonucleotide.

2. The oligonucleotide delivery enhancing compound according to claim 1, having a structure represented by formula AI or formula AII. 【Chemistry 1】 (Here, 【Chemistry 2】 Each of these independently represents a single or double covalent bond; X is an atom selected from the group consisting of carbon, nitrogen, oxygen, and sulfur at each of its occurrences; Each of F, G, H, and I is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; Here, m is an integer between 1, 2, and 3, and n is an integer between 1, 2, and 3, and m + n = 4; Here, C is either absent at each occurrence, or is a hydrogen atom, halogen atom, hydroxyl atom, (C 1 -C 20 ) alkyl, (C 1 -C 20 ) Alkyl, halogenated (C 1 -C 20 ) alkyl and halogenated (C 1 -C 20 ) Selected from the group consisting of alkoxys; Here, B is independently selected from the group consisting of, at each occurrence: hydroxyl, -C(O)OH, -P(O) 2 -OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C 1 -C 22 )alkyl, -(C 1 -C 22 )alkenyl, -(C 1 -C 22 )alkylene-OH, -(C 3 -C 22 )cycloalkylene-OH, -(C 6 -C 22 )arylene-OH, -(C 6 -C 22 )heteroarylene-OH, -(C 1 -C 22 )alkylene-C(O)OH, -(C 3 -C 22 )cycloalkylene-C(O)OH, -(C 6 -C 22 )arylene-C(O)OH, -(C 5 -C 22 )heteroarylene-C(O)OH, -O-C(O)-(C 1 -C 22 )alkylene-C(O)NH 2 , -(C 1 -C 22 )alkylene-O-C(O)-(C 1 -C 22 )alkylene-C(O)NH 2 , -O-C(O)-(C 1 -C 22 )alkylene-C(O)OH, -(C 1 -C 22 )alkylene-O-C(O)-(C 1 -C 22 )alkylene-C(O)OH, -C(O)-(C 1 -C 22 )alkylene-C(O)NH 2 , -(C 1 -C 22 )alkylene-C(O)-(C 1 -C 22 ) Alkylene-C(O)NH 2 , -C(O)-NH-(C 1 -C 22 ) Alkylene-OH, -C(O)-NH-(C 1 -C 22 ) Alkylene-C(O)OH, -(C 1 -C 22 ) Alkylene-C(O)-NH-(C 1 -C 22 ) Alkylene-C(O)OH, -(C 1 -C 30 ) Alkylene-P(O) 2 -OH, -(C 1 -C 22 ) Alkylene-O-P(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkylene-CN, -(C 1 -C 22 ) Alkylene-O-P(-N(C 1 -C 22 Alkyl) 2 [[ID=4​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​)alkylene-CN, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-CN, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-OH, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-C(O)OH, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 ) Alkylene -P(O)-OH, -(C 1 -C 22 )alkylene-P(O)(S)-OH, -(C 1 -C 22 ) Alkilen-CN; Here, A 1 , A 2 , and A 3 Each of these substituents is either absent or independently selected from the group consisting of: -H, -OH, -OR 1 , -SH, -(C 1 -C 25 )alkyl, halogenated -(C 1 -C 25 )alkyl, -(C 2 -C 22 ) Alkenil, -(C 1 -C 22 )alkylene-OH, -(C 3 -C 22 )cycloalkyl, -(C 3 -C 22 )Cycloalkenyl, -(C 1 -C 22 )Alkilen-(C 3 -C 22 )cycloalkyl, -(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 ) Alkilen-OR 1 , -(C 1 -C 22 ) Alkilen-COOR 1 , -C(O)OR 1 , -O-(C 1 -C 22 )alkyl, -S-(C 1 -C 22 )alkyl, -C(O)-R 1 , -C(O)-(C 1 -C 22 )alkyl, -OC(O)-(C 1 -C 22 )alkyl, -OC(O)-R 1 , -(C 1 -C 22 ) Alkylene-OC(O)-R 1 , -C(O)-(C 1 -C 22 )alkylene-OH, -C(O)-(C 1 -C 22 ) Alkilen-R 1 , -C(O)-(C 1 -C 22 ) Alkilen-NH-R 1 , -C(O)-(C 1 -C 22 ) Alkilen-NR 2 -R 1 , -OC(O)-(C 1 -C 22 )alkylene-OH, -OC(O)-(C 1 -C 22 ) Alkilen-R 1 , -Adamantyl, -(C 1 -C 22 )alkylene-adamantyl, -O-adamantyl, -C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )alkylene-C(O)-(C 1 -C 22 )alkylene-adamantyl, -NH-C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl, -(C 1 -C 22 )Alkylene-NH-C(O)-halogenation (C 1 -C 22 )alkyl, -CH(NH-CO-(C 1 -C 22 )alkyl)-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl, -C(O)-(C 1 -C 22 )alkylene-C(O)-NH-C[-(C 1 -C 22 ) Alkylene-O-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl] 3 , -C(O)-(C 1 -C 22 )alkylene-C(O)-NH-C[-(C 1 -C 22 ) Alkylene-O-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 ] 3 , -CH(NH-CO-halogenation (C 1 -C 22 )alkyl)-(C 1 -C 22 )Alkylene-NH-C(O)-halogenation (C 1 -C 22 )alkyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 ) Alkilen-NR 2 -C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )Alkilen-(C 1 -C 6 (Alkylene oxide) (1-20) -NH-C(O)-(C 1 -C 22 )alkylene-adamantyl, -C(O)NH-(C 1 -C 22 )alkyl, -C(O)NH-R 1 , -C(O)NR 2 -R 1 , -C(O)NH-(C 1 -C 22 )Alkylene-OH, -C(O)NH-(C 1 -C 22 )Alkylene-COOH, -NH-C(O)-(C 1 -C 22 )alkyl, -NH-C(O)-R 1 , -NR 2 -C(O)-R 1 , -OP(O) 2 -OR 1 , -OP(O)(S)-OR 1 , -OP(O)-OR 1 , -NH-R 1 , -NR 2 -R 1 , -(C 1 -C 22 ) Alkilen-NH-R 1 , -(C 1 -C 22 ) Alkilen-NR 2 -R 1 , -C(O)-(C 1 -C 22 ) Alkylene-C(O)-R 1 , -C(O)-(C 1 -C 22 )Alkylene-C(O)OR 1 , -C(O)-(C 1 -C 22 ) Alkilen-NH-C(O)-R 1 , -C(O)-(C 1 -C 22 ) Alkilen-NR 2 -C(O)-R 1 , -(C 1 -C 22 ) Alkylene-C(O)-R 1 , -(C 1 -C 22 ) Alkilen-NH-C(O)-R 1 , -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 ) Alkilen-NR 2 -C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-CN, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-OH, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-CN, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-CN, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-OH, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-C(O)OH, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 ) Alkylene -P(O)-OH, -(C 1 -C 22 )alkylene-P(O)(S)-OH, -(C 1 -C 22 ) alkylene-CN, substituted or unsubstituted pyrroles, substituted or unsubstituted pyrrolines, substituted or unsubstituted pyrrolidines, substituted or unsubstituted pyrazoles, substituted or unsubstituted pyrazolines, substituted or unsubstituted pyrazolidines, substituted or unsubstituted imidazoles, substituted or unsubstituted oxazoles, substituted or unsubstituted thiazoles, substituted or unsubstituted benzopyrroles, substituted or unsubstituted benzopyrrolines, substituted or unsubstituted benzopyrrolidines, substituted or unsubstituted benzopyrazoles, substituted or unsubstituted benzopyrazolines, substituted or unsubstituted benzopyrazolidines, substituted or unsubstituted benzimidazoles, substituted or unsubstituted benzoxazoles, substituted or unsubstituted benzothiazoles, and substituents represented by formula AIII; 【Transformation 3】 (Here, Y is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; each of P, Q, S, and T is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; the asterisk indicates the site where the substituent represented by formula AIII is bonded to the structure represented by formula AI or formula AII); Here, R 3 , R 4 , and R 5 Each of these substituents is either absent or independently selected from the group consisting of: -H, -OH, -OR 1 , -SH, -(C 1 -C 25 )alkyl, halogenated -(C 1 -C 25 )alkyl, -(C 2 -C 22 ) Alkenil, -(C 1 -C 22 )alkylene-OH, -(C 3 -C 22 )cycloalkyl, -(C 3 -C 22 )Cycloalkenyl, -(C 1 -C 22 )Alkilen-(C 3 -C 22 )cycloalkyl, -(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 ) Alkilen-OR 1 , -(C 1 -C 22 ) Alkilen-COOR 1 , -C(O)OR 1 , -O-(C 1 -C 22 )alkyl, -S-(C 1 -C 22 )alkyl, -C(O)-R 1 , -C(O)-(C 1 -C 22 )alkyl, -OC(O)-(C 1 -C 22 )alkyl, -OC(O)-R 1 , -(C 1 -C 22 ) Alkylene-OC(O)-R 1 , -C(O)-(C 1 -C 22 )alkylene-OH, -C(O)-(C 1 -C 22 ) Alkilen-R 1 , -C(O)-(C 1 -C 22 ) Alkilen-NH-R 1 , -C(O)-(C 1 -C 22 ) Alkilen-NR 2 -R 1 , -OC(O)-(C 1 -C 22 )alkylene-OH, -OC(O)-(C 1 -C 22 ) Alkilen-R 1 , -Adamantyl, -(C 1 -C 22 )alkylene-adamantyl, -O-adamantyl, -C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )alkylene-C(O)-(C 1 -C 22 )alkylene-adamantyl, -NH-C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl, -(C 1 -C 22 )Alkylene-NH-C(O)-halogenation (C 1 -C 22 )alkyl, -CH(NH-CO-(C 1 -C 22 )alkyl)-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl, -C(O)-(C 1 -C 22 )alkylene-C(O)-NH-C[-(C 1 -C 22 ) Alkylene-O-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl] 3 , -C(O)-(C 1 -C 22 )alkylene-C(O)-NH-C[-(C 1 -C 22 ) Alkylene-O-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 ] 3 , -CH(NH-CO-halogenation (C 1 -C 22 )alkyl)-(C 1 -C 22 )Alkylene-NH-C(O)-halogenation (C 1 -C 22 )alkyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 ) Alkilen-NR 2 -C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )Alkilen-(C 1 -C 6 (Alkylene oxide) (1-20) -NH-C(O)-(C 1 -C 22 )alkylene-adamantyl, -C(O)NH-(C 1 -C 22 )alkyl, -C(O)NH-R 1 , -C(O)NR 2 -R 1 , -C(O)NH-(C 1 -C 22 )Alkylene-OH, -C(O)NH-(C 1 -C 22 )Alkylene-COOH, -NH-C(O)-(C 1 -C 22 )alkyl, -NH-C(O)-R 1 , -NR 2 -C(O)-R 1 , -OP(O) 2 -OR 1 , -OP(O)(S)-OR 1 , -OP(O)-OR 1 , -NH-R 1 , -NR 2 -R 1 , -(C 1 -C 22 ) Alkilen-NH-R 1 , -(C 1 -C 22 ) Alkilen-NR 2 -R 1 , -C(O)-(C 1 -C 22 ) Alkylene-C(O)-R 1 , -C(O)-(C 1 -C 22 )Alkylene-C(O)OR 1 , -C(O)-(C 1 -C 22 ) Alkilen-NH-C(O)-R 1 , -C(O)-(C 1 -C 22 ) Alkilen-NR 2 -C(O)-R 1 , -(C 1 -C 22 ) Alkylene-C(O)-R 1 , -(C 1 -C 22 ) Alkilen-NH-C(O)-R 1 , -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 ) Alkilen-NR 2 -C(O)-(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-CN, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-OH, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-CN, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-CN, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-OH, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-C(O)OH, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 ) Alkylene -P(O)-OH, -(C 1 -C 22 )alkylene-P(O)(S)-OH, -(C 1 -C 22 ) Alkylene-CN, substituted or unsubstituted pyrroles, substituted or unsubstituted pyrrolines, substituted or unsubstituted pyrrolidines, substituted or unsubstituted pyrazoles, substituted or unsubstituted pyrazolines, substituted or unsubstituted pyrazolidines, substituted or unsubstituted imidazoles, substituted or unsubstituted oxazoles, substituted or unsubstituted thiazoles, substituted or unsubstituted benzopyrroles, substituted or unsubstituted benzopyrrolines, substituted or unsubstituted benzopyrrolidines, substituted or unsubstituted benzopyrazolines, substituted or unsubstituted benzopyrazolines, substituted or unsubstituted benzopyrazolines, substituted or unsubstituted benzoimidazoles, substituted or unsubstituted benzoxazoles, and substituted or unsubstituted benzothiazoles; Here, R 7 At each occurrence, it is bonded to one of P, Q, S, and T, and is either absent or contains hydrogen, a halogen atom, hydroxyl, or (C 1 -C 20 ) alkyl, (C 1 -C 20 ) Alkyl, halogenated (C 1 -C 20 ) alkyl and halogenated (C 1 -C 20 ) Selected from the group consisting of alkoxys; Here, M is an integer of 0, 1, 2, or 3; Here, R 6 It binds with one of P, Q, S, and T, and is selected from the following group: direct bond, -O-, -C(O)O-, -OC(O)-, -P(O) 2 -O-, -OP(O) 2 -O-, -P(O)(S)-O-, -OP(O)(S)-O-, -OP(O)-O-, -(C 1 -C 22 )Alkilen-, -(C 1 -C 22 ) Alkylene-O-, -O-(C 1 -C 22 )Alkilen-, -(C 1 -C 22 ) Alkylene-NH-, -NH-(C 1 -C 22 )Alkylene-, -C(O)-(C 1 -C 22 )Alkilen-, -(C 1 -C 22 ) Alkylene-C(O)-, -C(O)-O-(C 1 -C 22 )Alkilen-, -(C 1 -C 30 ) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 22 )alkylene-, -C(O)-NH-(C 1 -C 22 ) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 22 ) Alkylene-OC(O)-, -C(O)-NH-(C 1 -C 22 ) Alkylene-OC(O)-O-, -C(O)-NH-(C 1 -C 22 )Alkylene-O-, -C(O)-N((C 1 -C 22 )alkyl)-(C 1 -C 22 )Alkylene-, -C(O)-N((C 1 -C 22 )alkyl)-(C 1 -C 22 ) Alkylene-O-, -C(O)-NH-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-, -C(O)-NH-(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkylene-, -C(O)-NH-(C 1 -C 22 )alkylene-C(O)-NH-, -C(O)-N((C 1 -C 22 )alkyl)-(C 1 -C 22 )alkylene-C(O)-N((C 1 -C 22 )alkyl)-(C 1 -C 22 )Alkylene-, -C(O)-N((C 1 -C 22 )alkyl)-(C 1 -C 22 )alkylene-C(O)-N((C 1 -C 22 )alkyl)-, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkilen-, -(C 1 -C 22 )alkylene-C(O)-NH-(C 1 -C 22 )Alkylene-C(O)-NH-, -NH-C(O)-(C 1 -C 22 )Alkylene-, -NH-C(O)-(C 1 -C 22 )Alkylene-C(O)-O-, -NH-C(O)-(C 1 -C 22 ) Alkylene-C(O)-, -NH-C(O)-(C 1 -C 22 )Alkylene-O-, -N((C 1 -C 22 )(alkyl)-C(O)-(C 1 -C 22 )(alkylene)-, -N((C 1 -C 22 )(alkyl)-C(O)-(C 1 -C 22 )(alkylene)-O-, -NH-C(O)-(C 1 -C 22 )(alkylene)-NH-C(O)-(C 1 -C 22 )(alkylene)-, -NH-C(O)-(C 1 -C 22 )(alkyl)-C(O)-, -N((C 1 -C 22 )(alkyl)-C(O)-(C 1 -C 22 )(alkylene)-N((C 1 -C 22 )(alkyl)-C(O)-(C 1 -C 22 )(alkylene)-, -N((C 1 -C 22 )(alkyl)-C(O)-(C 1 -C 22 )(alkylene)-N((C 1 -C 22 )(alkyl)-C(O)-, -(C 1 -C 22 )(alkylene)-NH-C(O)-(C 1 -C 22 )(alkylene)-NH-C(O)-(C 1 -C 22 )(alkylene)-, -(C 1 -C 22 )(alkylene)-NH-C(O)-(C 1 ​​​​​​​​​​​​​​​​​​​​​ 22 )Cycloalkylene-O-,-O-(C 3 -C 22 )Cycloalkylene-,-(C 6 -C 22 )Ariren-, -(C 6 -C 22 )Arirene-O-, -O-(C 6 -C 22 )Ariren-, -(C 6 -C 22 ) Arylene-NH-, -NH-(C 6 -C 22 )Arirene-, -C(O)-(C 6 -C 22 )Ariren-, -(C 6 -C 22 )Arirene-C(O)-, -C(O)-O-(C 6 -C 22 )Ariren-, -(C 6 -C 22 )Arirene-C(O)-O-, -C(O)-NH-(C 6 -C 22 )Arylene- and -C(O)-NH-(C 6 -C 22 )Arirene-C(O)-O-; Here, R 1 is independently selected from the group consisting of, at each occurrence: hydrogen, hydroxyl, -(C 1 -C 22 )alkyl, -(C 3 -C 22 )cycloalkyl, -(C 6 -C 22 )aryl, -(C 1 -C 22 )alkoxy, -(C 3 -C 22 )cycloalkoxy, -(C 6 -C 22 )aryloxy, -C(O)-(C 1 -C 22 )alkyl, -OC(O)(C 1 -C 22 )alkyl, -C(O)-O-(C 1 -C 22 )alkyl, -C(O)-(C 3 -C 22 )cycloalkyl, -OC(O)-(C 3 -C 22 )cycloalkyl, -C(O)-O-(C 3 -C 22 )cycloalkyl, -C(O)-(C 6 -C 22 )aryloxy, -OC(O)-(C 6 -C 22 )aryloxy, -C(O)-O-(C 6 -C 22 )aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, glucosyl, acetamidoglucosyl, galactosamine, N-acetylgalactosamine, lipid, PEG, steroid, lipophilic group, carbohydrate, cholesterol, adamantane, amino acid, peptide, chloroquine and alkaloid; Here, R 2 At each occurrence, the halogen atom, (C 1 -C 12 ) alkyl, (C 1 -C 12 )alkoxy, (C 1 -C 12 )alkoxycarbonyl, (C 6 -C 16 )aryl, or (C 6 -C 16 ) Independently selected from the group consisting of aryloxycarbonyls; A 1 , A 2 , A 3 B, C, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 One or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained therein are optionally bonded to the supporting material or protected by end-protecting groups; However, A 1 , A 2 and A 3 But at the same time, not hydrogen, R 3 , R 4 and R 5 (However, this is conditional on it not being hydrogen.)

3. The oligonucleotide delivery enhancing compound according to claim 1, comprising a substructure represented by formula BI and at least one substituent that can be directly or indirectly bound to an oligonucleotide. 【Chemistry 4】 (Here, X' is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; each of F', G', H', and I' is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; each of the asterisks refers to a site that can arbitrarily bind directly or indirectly to at least one substituent or oligonucleotide.)

4. The oligonucleotide delivery enhancing compound according to claim 3, having a structure represented by formula BII. 【Transformation 5】 (Here, X' is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; Each of F', G', H', and I' is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; Here, A1', A2', and A3' are either absent or independently selected substituents from the group consisting of: -H, -R 1 ', -OR 1 ', -SR 1 ', -C(O)-R 1 ', -C(O)OR 1 ', -OC(O)-R 1 ', -C(O)NH-R 1 ', -C(O)NR 2 '-R 1 ', -NH-C(O)-R 1 ', -NR 2 '-C(O)-R 1 ', -OP(O) 2 -OR 1 ', -OP(O)(S)-OR 1 ', -OP(O)-OR 1 ', -NH-R 1 ', -NR 2 '-R 1 ', -(CH 2 ) r’ -NH-R 1 ', -(CH 2 ) r’ -NR 2 '-R 1 ', -C(O)-(CH 2 ) r’ -R 1 ', -C(O)-(CH 2 ) r’ -NH-R 1 ', -C(O)-(CH 2 ) r’ -NR 2 '-R 1 ', -C(O)-(CH 2 ) r’ -C(O)-R 1 ', -C(O)-(CH 2 ) r’ -C(O)OR 1 ', -C(O)-(CH 2 ) r’ -NH-C(O)-R 1 ', -C(O)-(CH 2 ) r’ -NR 2 ’-C(O)-R 1 ’, -(CH 2 ) r’ -C(O)-R 1 ’; -(CH 2 ) r’ -C(O)O-R 1 ’; -(CH 2 ) r’ -O-C(O)-R 1 ’, -(CH 2 ) r’ -R 1 ’, -(CH 2 ) r’ -NH-C(O)-R 1 ’, -(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -NH-C(O)-(C 1 -C 22 )アルキレン-NH-C(O)-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -C(O)-NH-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -C(O)- NH-(C 1 -C 22 )アルキレン-C(O)-NH-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -C(O)-NH-(C 1 -C 22 )アルキレン-NH-C(O)-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -NR 2 ’-C(O)-(CH 2 ) s’ -R 1 ’, -CH(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -C(O)-NH-(CH 2 ) s’ -R 1 ’)(-C(O)-NH-(CH 2 ) q’ -R 3 ’), -N(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-(CH 2 ) p’ -NH-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-(CH 2 ) p’ -NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')(-NR 6 '-C(O)-(CH 2 ) q’ -R 3 '), -CH(-(CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')(-(CH 2 ) p’ -NR 6 '-C(O)-(CH 2 ) q’ -R 3 '), -CR 4 '((CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')((CH 2 ) p’ -NR 6 '-C(O)-(CH 2 ) q’ -R 3 '), -CR 4 '((CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')((CH 2 ) p’ -NR 6 '-C(O)-(CH 2 ) q’ -R 3 '), or A1' and A2' bond to each other to form an unsubstituted or substituted heterocycle with A1', A2', the nitrogen atom bonded to A1', and the carbon atom bonded to A2'; Here, each of R1' and R3' is independently selected from the group consisting of: hydrogen, hydroxyl, -(C 1 -C 30 )alkyl, -(C 3 -C 50 )cycloalkyl, -(C 6 -C 50 )aryl, -(C 1 -C 30 )alkoxy, -(C 3 -C 50 )cycloalkoxy, -(C 6 -C 50 )aryloxy, -C(O)-(C 1 -C 30 )alkyl, -OC(O)(C 1 -C 30 )alkyl, -C(O)-O-(C 1 -C 30 )alkyl, -C(O)-(C 3 -C 50 )cycloalkyl, -OC(O)-(C 3 -C 50 )Cycloalkyl, -C(O)-O-(C 3 -C 50 )Cycloalkyl, -C(O)-(C 6 -C 50 )aryloxy, -OC(O)-(C 6 -C 50 )aryloxy, -C(O)-O-(C 6 -C 50 )aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, glucosyl, acetamidoglucosyl, galactosamine, N-acetylgalactosamine, lipids, PEG, steroids, lipophilic groups, carbohydrates, cholesterol, adamantane, amino acids, peptides, ligands, nucleic acids, oligonucleotides, aptamers, small molecules, antibodies, antibody fragments, chloroquine, alkaloids and target sites, where one or more hydroxyl groups, carboxyl groups and amino groups contained in R1' and R3' respectively are optionally protected; Here, each of R2', R4', R5', and R6' is independently a halogen atom, (C 1 -C 12 ) alkyl, (C 1 -C 12 )alkoxy, (C 1 -C 12 )alkoxycarbonyl, (C 6 -C 16 )aryl or (C 6 -C 16 ) It is an aryloxycarbonyl; Here, r', s', p', and q' are integers from 1 to 22, and are conditional on the fact that if X' is oxygen, then A3' does not exist, and A1', A2', and A3' are not hydrogen at the same time; Here, each C' is bonded to one of F', G', H', and I', either absent or hydrogen, halogen atom, hydroxyl, (C 1 -C 20 ) alkyl, (C 1 -C 20 ) Alkyl, halogenated (C 1 -C 20 ) alkyl and halogenated (C 1 -C 20 ) Selected from the group consisting of alkoxys; Here, m' is an integer of 1, 2, or 3, n' is an integer of 1, 2, or 3, and m' + n' = 4; Here, each B' is bonded to one of F', G', H', and I', and is independently selected from the group consisting of: hydroxyl, -C(O)OH, -(C 1 -C 30 )alkoxy, -P(O) 2 -OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C 1 -C 30 )alkylene-OH, -(C 3 -C 50 )Cycloalkylene-OH, -(C 6 -C 50 ) Arylene-OH, -(C 5 -C 50 )heterorialene-OH, -(C 1 -C 30 )alkylene-C(O)OH, -(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 6 -C 50 )Arylene-C(O)OH, -(C 5 -C 50 )heterorylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-[(C 1 -C 30 )Alkilen-O] r’ -H (where r' is an integer from 1 to 22), -C(O)-NH-[(C 1 -C 30 )Alkilen-O] r’ -(C 1 -C 30 )alkylene-C(O)-OH (where r' is an integer from 1 to 22), -C(O)-NH-(C 3 -C 50 )Cycloalkylene-OH, -C(O)-NH-(C 6 -C 50 )Arylene-OH, -C(O)-NH-(C 5 -C 50 )heterorialene-OH,-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkilen-(C 6 -C 50 )Ariren-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 ) Alkylene-P(O) 2 -OH, -(C 3 -C 50 )Cycloalkylene-P(O) 2 -OH, -(C 6 -C 50 ) Arirene-P(O) 2 -OH, -(C 5 -C 50 ) Heteroarylene-P(O) 2 -OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-CN, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-CN, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 ) Alkylene -P(O)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)-OH, -(C 6 -C 50 )Arylene-P(O)-OH, -(C 5 -C 50 ) -heterorylene-P(O)-OH, -(C 1 -C 30 )alkylene-P(O)(S)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)(S)-OH, -(C 6 -C 50 )Arylene-P(O)(S)-OH, -(C 5 -C 50 )heterorylene-P(O)(S)-OH, -(C 1 -C 30 )Alkylene-CN, -(C 3 -C 50 )Cycloalkylene-CN,-(C 6 -C 50 )Arirene-CN, -(C 5 -C 50 ) Heteroarylene-CN, lipids, PEG, steroids, lipophilic groups, carbohydrates, cholesterol, adamantane, amino acids, peptides, chloroquine, alkaloids, and substituents represented by formula BIII: 【Transformation 6】 (Here, Y' is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; each of P', Q', S', and T' is independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur; the asterisk indicates the site where the substituent represented by formula BIII is bonded to one of F', G', H', and I' of formula BII) Here, R7' is selected from the following group: -O-, -C(O)O-, -OC(O)-, -P(O) 2 -O-, -OP(O) 2 -O-, -P(O)(S)-O-, -OP(O)(S)-O-, -OP(O)-O-, -(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-O-, -O-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-NH-, -NH-(C 1 -C 30 )Alkylene-, -C(O)-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-C(O)-, -C(O)-O-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 30 )alkylene-, -C(O)-NH-(C 1 -C 30 ) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 30 ) Alkylene-OC(O)-, -C(O)-NH-(C 1 -C 30 ) Alkylene-OC(O)-O-, -C(O)-NH-(C 1 -C 30 )Alkylene-O-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )Alkylene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 ) Alkylene-O-, -C(O)-NH-(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-, -C(O)-NH-(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )alkylene-, -C(O)-NH-(C 1 -C 30 )alkylene-C(O)-NH-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )alkylene-C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )Alkylene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )alkylene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkylene-C(O)-NH-, -NH-C(O)-(C 1 -C 30 )Alkylene-, -NH-C(O)-(C 1 -C 30 )Alkylene-C(O)-O-, -NH-C(O)-(C 1 -C 30 ) Alkylene-C(O)-, -NH-C(O)-(C 1 -C 30 )Alkylene-O-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 ) Alkylene-O-, -NH-C(O)-(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )Alkylene-, -NH-C(O)-(C 1 -C 30 )alkylene-NH-C(O)-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-N((C 1 -C 20 )alkyl)-C(O)-, -(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )Alkylene-NH-C(O)-, -(C 1 -C 30 ) Alkilen -P(O) 2 -O-, -(C 1 -C 30 Alkilen-OP(O) 2 -O-, -(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-O-,-O-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-NH-,-NH-(C 3 -C 50 )Cycloalkylene-, -C(O)-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-C(O)-, -C(O)-O-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-C(O)-O-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-O-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-O-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-O-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 ) Cycloalkylene-, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-,-(C 3 -C 50 )Cycloalkylene -P(O) 2 -O-, -(C 3 -C 50 )Cycloalkylene-OP(O) 2 -O-, -(C 6 -C 50 )Ariren-, -(C 6 -C 50 )Arirene-O-, -O-(C 6 -C 50 )Ariren-, -(C 6 -C 50 ) Arylene-NH-, -NH-(C 6 -C 50 )Arirene-, -C(O)-(C 6 -C 50 )Ariren-, -(C 6 -C 50 )Arirene-C(O)-, -C(O)-O-(C 6 -C 50 )Ariren-, -(C 6 -C 50 )Arirene-C(O)-O-, -C(O)-NH-(C 6 -C 50 )Arirene-, -C(O)-NH-(C 6 -C 50 )Arirene-C(O)-O-, -C(O)-NH-(C 6 -C 50 )Arirene-O-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arirene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arirene-O-, -C(O)-NH-(C 6 -C 50 )Arirene-C(O)-NH-(C 3 -C 50 ) Cycloalkylene-, -C(O)-NH-(C 6 -C 50 )Arylene-C(O)-NH-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arylene-C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arirene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arylene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 6 -C 50 )Arirene-C(O)-NH-(C 6 -C 50 )Arirene-C(O)-NH-(C 6 -C 50 ) Ariren-, -(C 6 -C 50 )Arirene-C(O)-NH-(C 6 -C 50 )Arirene-C(O)-NH-, -(C 6 -C 50 ) Ariren -P(O) 2 -O-, -(C 6 -C 50 ) Arirene-OP(O) 2 -O-, -(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorialene-O-, -O-(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorylene-NH-,-NH-(C 5 -C 50 )heterorialene-, -C(O)-(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorialene-C(O)-, -C(O)-O-(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorialene-C(O)-O-, -C(O)-NH-(C 5 -C 50 )heterorialene-, -C(O)-NH-(C 5 -C 50 )heterorialene-C(O)-O-, -C(O)-NH-(C 5 -C 50 )heterorialene-O-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-O-, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)-NH-(C 3 -C 50 ) Cycloalkylene-, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)-NH-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 5 -C 50 )heterorylene-C(O)-NH-(C 5 -C 50 )heterorylene-C(O)-NH-(C 6 -C 50 ) Ariren-, -(C 5 -C 50 )heterorylene-C(O)-NH-(C 5 -C 50 )heterorialene-C(O)-NH-, -(C 5 -C 50 ) Heteroarylene -P(O) 2 -O-, -(C 5 -C 50 ) Heteroarylene-OP(O) 2 -O-; Here, R8' and R9' are either absent or substituents independently selected from the group consisting of: -H, hydroxyl, -(C 1 -C 30 )alkyl, -(C 3 -C 50 )cycloalkyl, -(C 6 -C 50 )aryl, -(C 1 -C 30 )alkylene-OH, -(C 3 -C 50 )Cycloalkylene-OH, -(C 6 -C 50 ) Arylene-OH, -(C 1 -C 30 )alkylene-C(O)OH, -(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 6 -C 50 )Arylene-C(O)OH, -(C 1 -C 30 ) Alkilen-NH 2 , -(C 3 -C 50 ) Cycloalkylene-NH 2 , -(C 6 -C 50 ) Arylene-NH 2 , -(C 1 -C 30 )alkoxy, -(C 3 -C 50 )cycloalkoxy, -(C 6 -C 50 )aryloxy, -C(O)-(C 1 -C 30 )alkyl, -OC(O)(C 1 -C 30 )alkyl, -C(O)-O-(C 1 -C 30 )alkyl, -C(O)-(C 3 -C 50 )cycloalkyl, -OC(O)-(C 3 -C 50 )Cycloalkyl, -C(O)-O-(C 3 -C 50 )Cycloalkyl, -C(O)- (C 6 -C 50 )aryloxy, -OC(O)-(C 6 -C 50 )aryloxy, -C(O)-O-(C 6 -C 50 )aryloxy, -C(O)-NH-(C 1 -C 30 )alkyl, -C(O)-NH-(C 3 -C 50 )Cycloalkyl, -C(O)-NH-(C 6 -C 50 )aryl, -(C 1 -C 30 )Alkylene-phosphate, -(C 3 -C 50 )Cycloalkylene-phosphate, -(C 6 -C 50 ) Arylene-phosphate; Here, R 8 'and R 9 One or more hydroxyl groups, carboxyl groups, amino groups, and phosphate groups contained in each of ' are optionally protected by a terminal protecting group, or R 8 ' and R9' combine with each other, R 8 ', R 9 ', R 8 ' and the carbon atom bonded to R 9 The Y' atom bonded to ' forms an unsubstituted or substituted heterocycle; however, if Y' is oxygen or sulfur, then R9' does not exist; Each R 10 ' is bound to one of P', Q', S', and T' and is independently selected from the group consisting of: hydroxyl, C(O)OH, -P(O) 2 -OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C 1 -C 30 )alkylene-OH, -(C 3 -C 50 )Cycloalkylene-OH, -(C 6 -C 50 ) Arylene-OH, -(C 5 -C 50 )heterorialene-OH, -(C 1 -C 30 )alkylene-C(O)OH, -(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 6 -C 50 )Arylene-C(O)OH, -(C 5 -C 50 )heterorylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-OH, -C(O)-NH-(C 6 -C 50 )Arylene-OH, -C(O)-NH-(C 5 -C 50 )heterorialene-OH,-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 ) Alkylene-C(O)NH 2 , -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 )alkylene-OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 ) Alkylene-P(O) 2 -OH, -(C 3 -C 50 )Cycloalkylene-P(O) 2 -OH, -(C 6 -C 50 ) Arirene-P(O) 2 -OH, -(C 5 -C 50 ) Heteroarylene-P(O) 2 -OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-CN, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-CN, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 ) Alkylene -P(O)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)-OH, -(C 6 -C 50 )Arylene-P(O)-OH, -(C 5 -C 50 ) -heterorylene-P(O)-OH, -(C 1 -C 30 )alkylene-P(O)(S)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)(S)-OH, -(C 6 -C 50 )Arylene-P(O)(S)-OH, -(C 5 -C 50 )heterorylene-P(O)(S)-OH, -(C 1 -C 30 )Alkylene-CN, -(C 3 -C 50 )Cycloalkylene-CN,-(C 6 -C 50 )Arirene-CN, -(C 5 -C 50 ) Heteroarylene-CN, where R 10 One or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in ' are optionally bonded to the supporting material or protected by end-protecting groups; Here, each R 11 It is bonded to one of P', Q', S', and T', and is either absent or contains hydrogen, a halogen atom, hydroxyl, (C 1 -C 20 ) alkyl, (C 1 -C 20 ) Alkyl, (C 1 -C 20 ) Alkoxycarbonyl, halogenated (C 1 -C 20 ) alkyl and halogenated (C 1 -C 20 ) Selected from the group consisting of alkoxycarbonyls; Here, M' is an integer of 1, 2, or 3, N' is an integer of 1, 2, or 3, and M' + N' = 4.

5. One or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in each of A1, A2, A3, B, C, R1, R2, R3, R4, R5, and R6 are optionally protected by a terminal protecting group RP selected from the group consisting of (C1-C22)alkyl, (C1-C22)alkoxy, (C1-C22)alkylcarbonyl, (C1-C22)alkoxycarbonyl, (C6-C22)aryl, (C6-C22)aryloxy, (C6-C22)arylcarbonyl, (C6-C22)allyloxycarbonyl, glucosyl, acetamidoglucosyl, galactosamine, N-acetylgalactosamine, tri((C1-C22)alkyl)silyl, and tri((C1-C22)alkoxy)silyl. Here, the supporting material is selected from the group consisting of silica, silica gel, glass, ceramic, polymer, cellulose, and combinations thereof. The oligonucleotide delivery enhancing compound according to claim 2.

6. One or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups and phosphate groups contained in each of R1', R2', R3', R4', R5', R6', R7', R8', R9', R10' and R11' are optionally protected by a terminal protecting group RP selected from the group consisting of (C1-C22)alkyl, (C1-C22)alkoxy, (C1-C22)alkylcarbonyl, (C1-C22)alkoxycarbonyl, (C6-C22)aryl, (C6-C22)aryloxy, (C6-C22)arylcarbonyl, (C6-C22)allyloxycarbonyl, glucosyl, acetamidoglucosyl, galactosamine, N-acetylgalactosamine, tri((C1-C22)alkyl)silyl and tri((C1-C22)alkoxy)silyl, Here, the supporting material is selected from the group consisting of silica, silica gel, glass, ceramic, polymer, cellulose, and combinations thereof. The oligonucleotide delivery enhancer compound according to claim 4.

7. The oligonucleotide delivery enhancing compound according to claim 2, having a structure represented by any one of formulas AIV to AXIII and formulas BIV to BXIV. 【Transformation 7】 【Transformation 8】 (Here, A 1 , A 2 , A 3 , A 4 , F, G, H, I, B, C, P, Q, S, T, R 6 , R 7 , m, n, and M are as defined in claim 2; Here, each of ring I and ring II is a 4, 5, 6, 7, 8, or 9-membered ring; Here, A4' is bonded to any atom of ring I, and each of A4', A5', and A6' is independently selected from the group consisting of: -R 1 ', -OR 1 ', -SR 1 ', -C(O)-R 1 ', -C(O)OR 1 ', -OC(O)-R 1 ', -C(O)NH-R 1 ', -C(O)NR 2 '-R 1 ', -NH-C(O)-R 1 ', -NR 2 '-C(O)-R 1 ', -OP(O) 2 -OR 1 ', -OP(O)(S)-OR 1 ', -OP(O)-OR 1 ', -NH-R 1 ', -NR 2 '-R 1 ', -(CH 2 ) r’ -NH-R 1 ', -(CH 2 ) r’ -NR 2 '-R 1 ', -C(O)-(CH 2 ) r’ -R 1 ', -C(O)-(CH 2 ) r’ -NH-R 1 ', -C(O)-(CH 2 ) r’ -NR 2 '-R 1 ', -C(O)-(CH 2 ) r’ -C(O)-R 1 ', -C(O)-(CH 2 ) r’ -C(O)OR 1 ', -C(O)-(CH 2 ) r’ -NH-C(O)-R 1 ', -C(O)-(CH 2 ) r’ -NR 2 ’-C(O)-R 1 ’, -(CH 2 ) r’ -C(O)-R 1 ’; -(CH 2 ) r’ -C(O)O-R 1 ’; -(CH 2 ) r’ -O-C(O)-R 1 ’, -(CH 2 ) r’ -R 1 ’, -(CH 2 ) r’ -NH-C(O)-R 1 ’, -(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -NR 2 ’-C(O)-(CH 2 ) s’ -R 1 ’, -CH(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -N(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-(CH 2 ) p’ -NH-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-(CH 2 ) p’ -NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -NR 5 ’-C(O)-(CH 2 ) s’ -R 1 ’)(-NR 6 ’-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -NR 5 ’-C(O)-(CH 2 ) s’ -R 1 ’)(-(CH 2 ) p’ -NR 6 ’-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’((CH 2 ) r’ -NR 5 ’-C(O)-(CH 2 ) s’ -R 1 ’)((CH 2 ) p’ -NR 6 ’-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’((CH 2 ) r’ -NR 5 ’-C(O)-(CH 2 ) s’ -R 1 ’)((CH 2 ) p’ -NR 6 ’-C(O)-(CH 2 ) q’ -R 3 ’); Here, each of R1' and R3' is independently selected from the group consisting of: hydrogen, hydroxyl, -(C 1 -C 30 )alkyl, -(C 3 -C 50 )cycloalkyl, -(C 6 -C 50 )aryl, -(C 1 -C 30 )alkoxy, -(C 3 -C 50 )cycloalkoxy, -(C 6 -C 50 )aryloxy, -C(O)-(C 1 -C 30 )alkyl, -OC(O)(C 1 -C 30 )alkyl, -C(O)-O-(C 1 -C 30 )alkyl, -C(O)-(C 3 -C 50 )cycloalkyl, -OC(O) -(C 3 -C 50 )Cycloalkyl, -C(O)-O-(C 3 -C 50 )Cycloalkyl, -C(O)- (C 6 -C 50 )aryloxy, -OC(O)-(C 6 -C 50 )aryloxy, -C(O)-O-(C 6 -C 50 ) Aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, lipid, PEG, steroid, lipophilic group, carbohydrate, cholesterol, adamantane, amino acid, peptide, ligand, nucleic acid, oligonucleotide, aptamer, small molecule, antibody, antibody fragment, polyethylene glycol, glycan, antibody, antibody fragment, chloroquine, alkaloid and target site; Here, one or more hydroxyl groups, carboxyl groups, and amino groups contained in R1' and R3' respectively are optionally protected; Here, each of R2', R4', R5', and R6' is independently a halogen atom, (C 1 -C 12 ) alkyl, (C 1 -C 12 )alkoxy, (C 6 -C 16 )aryl or (C 6 -C 16 ) It is an aryloxy; Here, r', s', p', and q' are integers from 1 to 22; Here, R 12 ' is bonded to any atom of ring II and is selected from the group consisting of -hydrogen, hydroxyl, -(C 1 -C 30 )alkyll, -(C 3 -C 50 )cycloalkyl, -(C 6 -C 50 )aryl, -(C 1 -C 30 )alkylene-OH, -(C 3 -C 50 )Cycloalkylene-OH, -(C 6 -C 50 ) Arylene-OH, -(C 1 -C 30 )alkylene-C(O)OH, -(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 6 -C 50 )Arylene-C(O)OH, -(C 1 -C 30 ) Alkilen-NH 2 , -(C 3 -C 50 ) Cycloalkylene-NH 2 , -(C 6 -C 50 ) Arylene-NH 2 , -(C 1 -C 30 )alkoxy, -(C 3 -C 50 )cycloalkoxy, -(C 6 -C 50 )aryloxy, -C(O)-(C 1 -C 30 )alkyll, -OC(O)(C 1 -C 30 )alkyll, -C(O)-O-(C 1 -C 30 )alkyll, -C(O)-(C 3 -C 50 )cycloalkyl, -OC(O)-(C 3 -C 50 )Cycloalkyl, -C(O)-O-(C 3 -C 50 )Cycloalkyl, -C(O)- (C 6 -C 50 )aryloxy, -OC(O)-(C 6 -C 50 )aryloxy, -C(O)-O-(C 6 -C 50 )aryloxy, -C(O)-NH-(C 1 -C 30 )alkyll, -C(O)-NH-(C 3 -C 50 )Cycloalkyl, -C(O)-NH-(C 6 -C 50 )aryl, -(C 1 -C 30 )Alkylene-phosphate, -(C 3 -C 50 )Cycloalkylene-phosphate, -(C 6 -C 50 ) Arylene-phosphate; where R 12 (One or more hydroxyl groups, carboxyl groups, amino groups, and phosphate groups contained in ' are optionally protected.)

8. The oligonucleotide delivery enhancing compound according to claim 2, F, G, H and I are carbon, m is 1 and n is 3, B is bonded to G or H, P, Q, S and T are carbon, R 6 It is coupled to either Q or S, Here, the protecting group R P This is selected from the group consisting of benzyloxycarbonyl (Cbz), tert-butyldimethylsilyl (TBS), 4,4'-dimethoxytrityl (DMTr), t-butyloxycarbonyl (Boc), benzyl (Bn), and benzyloxy (BnO). Here, C represents hydrogen, halogen atom, hydroxyl, (C) at each occurrence. 1 -C 12 ) alkyl, (C 1 -C 12 ) Alkyl, halogenated (C 1 -C 12 ) alkyl and halogenated (C 1 -C 12 ) Selected from the group consisting of alkoxys, Here, B is -(C 1 -C 22 )alkylene-OH, -OC(O)-(C 1 -C 16 ) Alkylene-C(O)NH 2 , -(C 1 -C 16 )alkylene-OC(O)-(C 1 -C 16 ) Alkylene-C(O)NH 2 , -OC(O)-(C 1 -C 16 )alkylene-C(O)OH, -(C 1 -C 16 )alkylene-OC(O)-(C 1 -C 16 )alkylene-C(O)OH, -C(O)-(C 1 -C 16 ) Alkylene-C(O)NH 2 , -(C 1 -C 16 )alkylene-C(O)-(C 1 -C 16 ) Alkylene-C(O)NH 2 , -C(O)-NH-(C 1 -C 16 )Alkylene-OH, -C(O)-NH-(C 1 -C 16 )alkylene-C(O)OH, -(C 1 -C 16 )alkylene-C(O)-NH-(C 1 -C 16 )alkylene-C(O)OH, -(C 1 -C 16 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 16 )Alkylene-CN, -(C 1 -C 16 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 16 )alkylene-OH, -(C 1 -C 16 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 16 ) Alkilen-NH 2 , -(C 1 -C 16 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 16 ) Alkylene-C(O)OH, and -C(O)-NH-(C 1 -C 16 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 16 ) Selected from the group consisting of alkylene-CN, Here, A 1 , A 2 , A 3 Each of these is either absent or -H, -OH, linear or branched -(C 6 -C 22 )alkyl, linear or branched-(C 2 -C 22 ) Alkenil, -(C 1 -C 22 )alkylene-OH, -(C 3 -C 22 )cycloalkyl, -(C 3 -C 22 )Cycloalkenyl, -(C 1 -C 22 )Alkilen-(C 3 -C 22 )cycloalkyl, -(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 ) Alkilen-OR 1 , -(C 1 -C 22 ) Alkilen-COOR 1 , -O-(C 1 -C 22 )alkyl, -(C 6 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 ) Alkilen-NR 2 -C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )Alkilen-(C 1 -C 6 (Alkylene oxide) (1-20) -NH-C(O)-(C 1 -C 22 )alkylene-adamantyl, -C(O)NH-R 1 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-CN, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-OH, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) A substituent independently selected from the group consisting of alkylene-CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzothiazole, and substituents represented by formula AIII. Here, Y is selected from the group consisting of carbon, nitrogen, oxygen, and sulfur, and each of P, Q, S, and T is carbon. Here, R 3 , R 4 , R 5 Each of these is either absent or -H, -OH, linear or branched -(C 6 -C 22 )alkyl, linear or branched-(C 2 -C 22 ) Alkenil, -(C 1 -C 22 )alkylene-OH, -(C 3 -C 22 )cycloalkyl, -(C 3 -C 22 )Cycloalkenyl, -(C 1 -C 22 )Alkilen-(C 3 -C 22 )cycloalkyl, -(C 1 -C 22 ) Alkilen-R 1 , -(C 1 -C 22 ) Alkilen-OR 1 , -(C 1 -C 22 ) Alkilen-COOR 1 , -O-(C 1 -C 22 )alkyl, -(C 6 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )alkyl, -(C 1 -C 22 )alkylene-NH-C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 ) Alkilen-NR 2 -C(O)-(C 1 -C 22 )Alkilen-adamantyl, -(C 1 -C 22 )Alkilen-(C 1 -C 6 (Alkylene oxide) (1-20) -NH-C(O)-(C 1 -C 22 )alkylene-adamantyl, -C(O)NH-R 1 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )Alkylene-CN, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-OH, -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) Alkilen-NH 2 , -(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 22 )Alkilen-OP(-N(C 1 -C 22 Alkyl) 2 )-O-(C 1 -C 22 ) A substituent independently selected from the group consisting of alkylene-CN, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrroline, substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyrazole, substituted or unsubstituted pyrazoline, substituted or unsubstituted pyrazolidine, substituted or unsubstituted imidazole, substituted or unsubstituted oxazole, substituted or unsubstituted thiazole, substituted or unsubstituted benzopyrrole, substituted or unsubstituted benzopyrroline, substituted or unsubstituted benzopyrrolidine, substituted or unsubstituted benzopyrazole, substituted or unsubstituted benzopyrazoline, substituted or unsubstituted benzopyrazolidine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, and substituted or unsubstituted benzothiazole; Here, R 7 At each occurrence, it is bonded to one of P, Q, S, and T, and is either absent or contains hydrogen, a halogen atom, hydroxyl, or (C 1 -C 20 ) alkyl, (C 1 -C 20 ) Alkyl, halogenated (C 1 -C 20 ) alkyl and halogenated (C 1 -C 20 ) Selected from the group consisting of alkoxys; Here, M is an integer of 0, 1, 2, or 3; Here, R 6 It combines with any of P, Q, S, and T, and -(C 1 -C 16 )Alkilen-, -(C 1 -C 16 ) Alkylene-O-, -O-(C 1 -C 16 )Alkilen-, -(C 1 -C 16 ) Alkylene-NH-, -NH-(C 1 -C 16 )Alkylene-, -C(O)-(C 1 -C 16 )Alkilen-, -(C 1 -C 16 ) Alkylene-C(O)-, -C(O)-O-(C 1 -C 16 )Alkilen-, -(C 1 -C16) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 16 )alkylene-, -C(O)-NH-(C 1 -C 16 ) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 16 ) Alkylene-OC(O)-, -C(O)-NH-(C 1 -C 16 ) Alkylene-OC(O)-O-, -C(O)-NH-(C 1 -C 16 )Alkylene-O-, -C(O)-N((C 1 -C 16 )alkyl)-(C 1 -C 16 )Alkylene-, -C(O)-N((C 1 -C 16 )alkyl)-(C 1 -C 16 ) Alkylene-O-, -C(O)-NH-(C 1 -C 16 )alkylene-C(O)-NH-(C 1 -C 16 )alkylene-, -C(O)-NH-(C 1 -C 16 )alkylene-NH-C(O)-(C 1 -C 16 )alkylene-, -C(O)-NH-(C 1 -C 16 )alkylene-C(O)-NH-, -C(O)-N((C 1 -C 16 )alkyl)-(C 1 -C 16 )alkylene-C(O)-N((C 1 -C 16 )alkyl)-(C 1 -C 16 )Alkylene-, -C(O)-N((C 1 -C 16 )alkyl)-(C 1 -C 16 )alkylene-C(O)-N((C 1 -C 16 )alkyl)-, -(C 1 -C 16 )alkylene-C(O)-NH-(C 1 -C 16 )alkylene-C(O)-NH-(C 1 -C 16 )Alkilen-, -(C 1 -C 16 )alkylene-C(O)-NH-(C 1 -C 16 )Alkylene-C(O)-NH-, -NH-C(O)-(C 1 -C 16 )Alkylene-, -NH-C(O)-(C 1 -C 16 )Alkylene-C(O)-O-, -NH-C(O)-(C 1 -C 16 ) Alkylene-C(O)-, -NH-C(O)-(C 1 -C 16 )Alkylene-O-, -N((C 1 -C 16 )alkyl)-C(O)-(C 1 -C 16 )Alkylene-, -N((C 1 -C 16 )alkyl)-C(O)-(C 1 -C 16 ) Alkylene-O-, -NH-C(O)-(C 1 -C 16 )alkylene-NH-C(O)-(C 1 -C 16 )Alkylene-, -NH-C(O)-(C 1 -C 16 )alkylene-NH-C(O)-, -N((C 1 -C 16 )alkyl)-C(O)-(C 1 -C 16 )Alkylene-N((C 1 -C 16 )alkyl)-C(O)-(C 1 -C 16 )Alkylene-, -N((C 1 -C 16 )alkyl)-C(O)-(C 1 -C 16 )Alkylene-N((C 1 -C 16 )alkyl)-C(O)-, -(C 1 -C 16 )alkylene-NH-C(O)-(C 1 -C 16 )alkylene-NH-C(O)-(C 1 -C 16 )Alkilen-, -(C 1 -C 16 )alkylene-NH-C(O)-(C 1 -C 16 A compound selected from the group consisting of alkylene-NH-C(O)- that enhances oligonucleotide delivery.

9. The oligonucleotide delivery enhancing compound according to claim 4, having a structure represented by any one of formulas BXV to BXXIX. 【Chemistry 9】 (Here, each of A1' and A2' is a substituent independently selected from the group consisting of: -R 1 ', -OR 1 ', -SR 1 ', -C(O)-R 1 ', -C(O)OR 1 ', -OC(O)-R 1 ', -C(O)NH-R 1 ', -C(O)NR 2 '-R 1 ', -NH-C(O)-R 1 ', -NR 2 '-C(O)-R 1 ', -OP(O) 2 -OR 1 ', -OP(O)(S)-OR 1 ', -OP(O)-OR 1 ', -NH-R 1 ', -NR 2 '-R 1 ', -(CH 2 ) r’ -NH-R 1 ', -(CH 2 ) r’ -NR 2 '-R 1 ', -C(O)-(CH 2 ) r’ -R 1 ', -C(O)-(CH 2 ) r’ -NH-R 1 ', -C(O)-(CH 2 ) r’ -NR 2 '-R 1 ', -C(O)-(CH 2 ) r’ -C(O)-R 1 ', -C(O)-(CH 2 ) r’ -C(O)OR 1 ', -C(O)-(CH 2 ) r’ -NH-C(O)-R 1 ', -C(O)-(CH 2 ) r’ -NR 2 '-C(O)-R 1 ’, -(CH 2 ) r’ -C(O)-R 1 ’; -(CH 2 ) r’ -C(O)O-R 1 ’; -(CH 2 ) r’ -O-C(O)-R 1 ’, -(CH 2 ) r’ -R 1 ’, -(CH 2 ) r’ -NH-C(O)-R 1 ’, -(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -NH-C(O)-(C 1 -C 22 )アルキレン-NH-C(O)-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -C(O)-NH-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -C(O)- NH-(C 1 -C 22 )アルキレン-C(O)-NH-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -C(O)-NH-(C 1 -C 22 )アルキレン-NH-C(O)-(CH 2 ) s’ -R 1 ’, -(CH 2 ) r’ -NR 2 ’-C(O)-(CH 2 ) s’ -R 1 ’, -CH(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -C(O)-NH-(CH 2 ) s’ -R 1 ’)(-C(O)-NH-(CH 2 ) q’ -R 3 ’), -N(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-(CH 2 ) p’ -NH-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-NH-C(O)-(CH 2 ) q’ -R 3 ’), -CR 4 ’(-(CH 2 ) r’ -NH-C(O)-(CH 2 ) s’ -R 1 ’)(-(CH 2 ) p’ -NH-C(O)-(CH 2 ) q’ -R 3 ’), -CH(-(CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')(-NR 6 '-C(O)-(CH 2 ) q’ -R 3 '), -CH(-(CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')(-(CH 2 ) p’ -NR 6 '-C(O)-(CH 2 ) q’ -R 3 '), -CR 4 '((CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')((CH 2 ) p’ -NR 6 '-C(O)-(CH 2 ) q’ -R 3 '), and -CR 4 '((CH 2 ) r’ -NR 5 '-C(O)-(CH 2 ) s’ -R 1 ')((CH 2 ) p’ -NR 6 '-C(O)-(CH 2 ) q’ -R 3 '); Here, R 1 'and R 3 Each of ' is independently selected from the group consisting of: hydrogen, hydroxyl -(C 1 -C 30 )alkyl, -(C 3 -C 50 )cycloalkyl, -(C 6 -C 50 )aryl, -(C 1 -C 30 )alkoxy, -(C 3 -C 50 )cycloalkoxy, -(C 6 -C 50 )aryloxy, -C(O)-(C 1 -C 30 )alkyl, -OC(O)(C 1 -C 30 )alkyl, -C(O)-O-(C 1 -C 30 )alkyl, -C(O)-(C 3 -C 50 )cycloalkyl, -OC(O)-(C 3 -C 50 )Cycloalkyl, -C(O)-O-(C 3 -C 50 )Cycloalkyl, -C(O)-(C 6 -C 50 )aryloxy, -OC(O)-(C 6 -C 50 )aryloxy, -C(O)-O-(C 6 -C 50 ) Aryloxy, -C(O)-phosphate ester group, phosphodiester group, phosphoramidite group, saturated fatty acid group, unsaturated fatty acid group, lipid, PEG, steroid, lipophilic group, carbohydrate, cholesterol, adamantane, amino acid, peptide, ligand, nucleic acid, oligonucleotide, aptamer, small molecule, antibody, antibody fragment, polyethylene glycol, antibody, antibody fragment, chloroquine, alkaloid and target site; R 1 'and R 3 One or more hydroxyl groups, carboxyl groups, and amino groups contained in each of ' are optionally protected; Here, R 2 ', R 4 ', R 5 'and R 6 Each of these is independently a halogen atom, (C 1 -C 12 ) alkyl, (C 1 -C 12 )alkoxy, (C 1 -C 12 )alkoxycarbonyl, (C 6 -C 16 )aryl or (C 6 -C 16 ) It is an aryloxycarbonyl; Here, r', s', p', and q' are integers from 1 to 22; Here, m' is an integer of 1, 2, or 3, n' is an integer of 1, 2, or 3, and m' + n' = 4; Here, each B' is independently selected from the group consisting of: hydroxyl, -C(O)OH, -(C 1 -C 30 )alkoxy, -P(O) 2 -OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C 1 -C 30 )alkylene-OH, -(C 3 -C 50 )Cycloalkylene-OH, -(C 6 -C 50 ) Arylene-OH, -(C 5 -C 50 )heterorialene-OH, -(C 1 -C 30 )alkylene-C(O)OH, -(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 6 -C 50 )Arylene-C(O)OH, -(C 5 -C 50 )heterorylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-[(C 1 -C 30 )Alkilen-O] r’ -H (where r' is an integer from 1 to 22), -C(O)-NH-[(C 1 -C 30 )Alkilen-O] r’ -(C 1 -C 30 )alkylene-C(O)-OH (where r' is an integer from 1 to 22), -C(O)-NH-(C 3 -C 50 )Cycloalkylene-OH, -C(O)-NH-(C 6 -C 50 )Arylene-OH, -C(O)-NH-(C 5 -C 50 )heterorialene-OH,-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkilen-(C 6 -C 50 )Ariren-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 ) Alkylene-P(O) 2 -OH, -(C 3 -C 50 )Cycloalkylene-P(O) 2 -OH, -(C 6 -C 50 ) Arirene-P(O) 2 -OH, -(C 5 -C 50 ) Heteroarylene-P(O) 2 -OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-CN, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-CN, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 ) Alkylene -P(O)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)-OH, -(C 6 -C 50 )Arylene-P(O)-OH, -(C 5 -C 50 ) -heterorylene-P(O)-OH, -(C 1 -C 30 )alkylene-P(O)(S)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)(S)-OH, -(C 6 -C 50 )Arylene-P(O)(S)-OH, -(C 5 -C 50 )heterorylene-P(O)(S)-OH, -(C 1 -C 30 )Alkylene-CN, -(C 3 -C 50 )Cycloalkylene-CN,-(C 6 -C 50 )Arirene-CN, -(C 5 -C 50 ) Heteroarylene-CN, lipids, PEG, steroids, lipophilic groups, carbohydrates, cholesterol, adamantane, amino acids, peptides, chloroquine, alkaloids; Here, each R7' is selected from the following group: -O-, -C(O)O-, -OC(O)-, -P(O) 2 -O-, -OP(O) 2 -O-, -P(O)(S)-O-, -OP(O)(S)-O-, -OP(O)-O-, -(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-O-, -O-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-NH-, -NH-(C 1 -C 30 )Alkylene-, -C(O)-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-C(O)-, -C(O)-O-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 ) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 30 )alkylene-, -C(O)-NH-(C 1 -C 30 ) Alkylene-C(O)-O-, -C(O)-NH-(C 1 -C 30 ) Alkylene-OC(O)-, -C(O)-NH-(C 1 -C 30 ) Alkylene-OC(O)-O-, -C(O)-NH-(C 1 -C 30 )Alkylene-O-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )Alkylene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 ) Alkylene-O-, -C(O)-NH-(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-, -C(O)-NH-(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )alkylene-, -C(O)-NH-(C 1 -C 30 )alkylene-C(O)-NH-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )alkylene-C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )Alkylene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 1 -C 30 )alkylene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkylene-C(O)-NH-, -NH-C(O)-(C 1 -C 30 )Alkylene-, -NH-C(O)-(C 1 -C 30 )Alkylene-C(O)-O-, -NH-C(O)-(C 1 -C 30 ) Alkylene-C(O)-, -NH-C(O)-(C 1 -C 30 )Alkylene-O-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 ) Alkylene-O-, -NH-C(O)-(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )Alkylene-, -NH-C(O)-(C 1 -C 30 )alkylene-NH-C(O)-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-, -N((C 1 -C 20 )alkyl)-C(O)-(C 1 -C 30 )Alkylene-N((C 1 -C 20 )alkyl)-C(O)-, -(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )Alkilen-, -(C 1 -C 30 )alkylene-NH-C(O)-(C 1 -C 30 )Alkylene-NH-C(O)-, -(C 1 -C 30 ) Alkilen -P(O) 2 -O-, -(C 1 -C 30 Alkilen-OP(O) 2 -O-, -(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-O-,-O-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-NH-,-NH-(C 3 -C 50 )Cycloalkylene-, -C(O)-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-C(O)-, -C(O)-O-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-C(O)-O-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-O-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-O-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-O-,-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 ) Cycloalkylene-, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-,-C(O)-N((C 1 -C 20 )alkyl)-(C 3 -C 50 )Cycloalkylene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-,-(C 3 -C 50 )Cycloalkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)-NH-,-(C 3 -C 50 )Cycloalkylene -P(O) 2 -O-, -(C 3 -C 50 )Cycloalkylene-OP(O) 2 -O-, -(C 6 -C 50 )Ariren-, -(C 6 -C 50 )Arirene-O-, -O-(C 6 -C 50 )Ariren-, -(C 6 -C 50 ) Arylene-NH-, -NH-(C 6 -C 50 )Arirene-, -C(O)-(C 6 -C 50 )Ariren-, -(C 6 -C 50 )Arirene-C(O)-, -C(O)-O-(C 6 -C 50 )Ariren-, -(C 6 -C 50 )Arirene-C(O)-O-, -C(O)-NH-(C 6 -C 50 )Arirene-, -C(O)-NH-(C 6 -C 50 )Arirene-C(O)-O-, -C(O)-NH-(C 6 -C 50 )Arirene-O-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arirene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arirene-O-, -C(O)-NH-(C 6 -C 50 )Arirene-C(O)-NH-(C 3 -C 50 ) Cycloalkylene-, -C(O)-NH-(C 6 -C 50 )Arylene-C(O)-NH-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arylene-C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arirene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 6 -C 50 )Arylene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 6 -C 50 )Arirene-C(O)-NH-(C 6 -C 50 )Arirene-C(O)-NH-(C 6 -C 50 ) Ariren-, -(C 6 -C 50 )Arirene-C(O)-NH-(C 6 -C 50 )Arirene-C(O)-NH-, -(C 6 -C 50 ) Ariren -P(O) 2 -O-, -(C 6 -C 50 ) Arirene-OP(O) 2 -O-, -(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorialene-O-, -O-(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorylene-NH-,-NH-(C 5 -C 50 )heterorialene-, -C(O)-(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorialene-C(O)-, -C(O)-O-(C 5 -C 50 )heterorialene-, -(C 5 -C 50 )heterorialene-C(O)-O-, -C(O)-NH-(C 5 -C 50 )heterorialene-, -C(O)-NH-(C 5 -C 50 )heterorialene-C(O)-O-, -C(O)-NH-(C 5 -C 50 )heterorialene-O-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-O-, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)-NH-(C 3 -C 50 ) Cycloalkylene-, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)-NH-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-, -C(O)-N((C 1 -C 20 )alkyl)-(C 5 -C 50 )heterorialene-C(O)-N((C 1 -C 20 )alkyl)-, -(C 5 -C 50 )heterorylene-C(O)-NH-(C 5 -C 50 )heterorylene-C(O)-NH-(C 6 -C 50 ) Ariren-, -(C 5 -C 50 )heterorylene-C(O)-NH-(C 5 -C 50 )heterorialene-C(O)-NH-, -(C 5 -C 50 ) Heteroarylene -P(O) 2 -O-, -(C 5 -C 50 ) Heteroarylene-OP(O) 2 -O-; Here, each R8' is a substituent independently selected from the group consisting of: -H, hydroxyl, -(C 1 -C 30 )alkyl, -(C 3 -C 50 )cycloalkyl, -(C 6 -C 50 )aryl, -(C 1 -C 30 )alkylene-OH, -(C 3 -C 50 )Cycloalkylene-OH, -(C 6 -C 50 ) Arylene-OH, -(C 1 -C 30 )alkylene-C(O)OH, -(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 6 -C 50 )Arylene-C(O)OH, -(C 1 -C 30 ) Alkilen-NH 2 , -(C 3 -C 50 ) Cycloalkylene-NH 2 , -(C 6 -C 50 ) Arylene-NH 2 , -(C 1 -C 30 )alkoxy, -(C 3 -C 50 )cycloalkoxy, -(C 6 -C 50 )aryloxy, -C(O)-(C 1 -C 30 )alkyl, -OC(O)(C 1 -C 30 )alkyl, -C(O)-O-(C 1 -C 30 )alkyl, -C(O)-(C 3 -C 50 )cycloalkyl, -OC(O)-(C 3 -C 50 )Cycloalkyl, -C(O)-O-(C 3 -C 50 )Cycloalkyl, -C(O)- (C 6 -C 50 )aryloxy, -OC(O)-(C 6 -C 50 )aryloxy, -C(O)-O-(C 6 -C 50 )aryloxy, -C(O)-NH-(C 1 -C 30 )alkyl, -C(O)-NH-(C 3 -C 50 )Cycloalkyl, -C(O)-NH-(C 6 -C 50 )aryl, -(C 1 -C 30 )Alkylene-phosphate, -(C 3 -C 50 )Cycloalkylene-phosphate, -(C 6 -C 50 ) Arylene-phosphate; Here, one or more hydroxyl groups, carboxyl groups, amino groups, and phosphate groups contained in each of R8 are optionally protected by terminal protecting groups; Here each R 10 ' is independently selected from the following group: hydroxyl, C(O)OH, -P(O) 2 -OH, -P(O)-OH, -P(O)(S)-OH, -CN, -(C 1 -C 30 )alkylene-OH, -(C 3 -C 50 )Cycloalkylene-OH, -(C 6 -C 50 ) Arylene-OH, -(C 5 -C 50 )heterorialene-OH, -(C 1 -C 30 )alkylene-C(O)OH, -(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 6 -C 50 )Arylene-C(O)OH, -(C 5 -C 50 )heterorylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-OH, -C(O)-NH-(C 6 -C 50 )Arylene-OH, -C(O)-NH-(C 5 -C 50 )heterorialene-OH,-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 ) Alkylene-C(O)NH 2 , -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 )alkylene-OC(O)-(C 1 -C 30 )alkylene-OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 3 -C 50 )Cycloalkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 6 -C 50 )Arylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 5 -C 50 )heterorylene-C(O)OH, -(C 1 -C 30 ) Alkylene-P(O) 2 -OH, -(C 3 -C 50 )Cycloalkylene-P(O) 2 -OH, -(C 6 -C 50 ) Arirene-P(O) 2 -OH, -(C 5 -C 50 ) Heteroarylene-P(O) 2 -OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-CN, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )Alkylene-CN, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 )alkylene-C(O)OH, -(C 1 -C 30 )alkylene-C(O)-NH-(C 1 -C 30 )Alkilen-OP(-N(C 1 -C 16 Alkyl) 2 )-O-(C 1 -C 30 ) Alkilen-NH 2 , -(C 1 -C 30 ) Alkylene -P(O)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)-OH, -(C 6 -C 50 )Arylene-P(O)-OH, -(C 5 -C 50 ) -heterorylene-P(O)-OH, -(C 1 -C 30 )alkylene-P(O)(S)-OH, -(C 3 -C 50 )Cycloalkylene-P(O)(S)-OH, -(C 6 -C 50 )Arylene-P(O)(S)-OH, -(C 5 -C 50 )heterorylene-P(O)(S)-OH, -(C 1 -C 30 )Alkylene-CN, -(C 3 -C 50 )Cycloalkylene-CN,-(C 6 -C 50 )Arirene-CN, -(C 5 -C 50 ) Heteroarylene-CN, where R 10 (One or more hydroxyl groups, carboxyl groups, amino groups, nitrile groups, and phosphate groups contained in ' are either optionally bonded to the supporting material or protected by end-protecting groups.)

10. The oligonucleotide delivery enhancing compound according to claim 2, having the following structure. 【Chemistry 10】 【Chemistry 11】 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 [Chemistry 18] 【Chemistry 19】 【Chemistry 20】 【Chemistry 21】 【Chemistry 22】 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 Here, 【Chemistry 26】 This represents the supporting material.

11. The oligonucleotide delivery enhancing compound according to claim 1, wherein at least one hydrogen atom contained in the oligonucleotide delivery enhancing compound is substituted with a deuterium atom.

12. An oligonucleotide delivery agent comprising a delivery-enhancing compound (DEC) moiety derivable from the oligonucleotide delivery-enhancing compound described in claim 1 and at least one oligonucleotide, The oligonucleotide delivery enhancement compound moiety is directly bonded to -O-, -S-, -C(O)-, -NH-, -N((C 1 -C 12 )alkyl)-, -N((C 1 -C 12 )alkyl)-C(O)-O-, -OC(O)-, -C(O)-O-, -OC(O)-O-, -C(O)-NH-, -OP(O) 2 O-, -OP(O)O-, -OP(O)(S)O-, -OS(O) 2 -O-, -S(O) 2 -O-, -S(O)-O-, -(C 1 -C 22 )Alkilen-, -(C 1 -C 22 ) Alkylene-NH-, -NH-(C 1 -C 22 )Alkilen-, -(C 1 -C 22 )Alkylene-NH-C(O)-, -(C 1 -C 22 ) Alkylene-C(O)-, -(C 1 -C 22 ) Alkylene-C(O)-O-, -C(O)-(C 1 -C 22 )Alkylene-, -NH-C(O)-(C 1 -C 22 )alkylene-, -C(O)-NH-(C 1 -C 22 )Alkylene-, -C(O)-(C 1 -C 22 ) Alkylene-NH-, -NH-(C 1 -C 22 ) Alkylene-C(O)-, -C(O)-(C 1 -C 22 ) Alkylene-C(O)-, -NH-(C 1 -C 22 )alkylene-NH-, -C(O)-(C 1 -C 22 ) Alkylene-C(O)O-, -OC(O)-(C 1 -C 22 ) Alkylene-C(O)-O-, -C(O)-O-(C 1 -C 22 ) Alkylene-OC(O)-, -C(O)-(C 1 -C 22 )Alkylene-NH-C(O)-, -NH-C(O)-(C 1 -C 22 ) Alkylene-C(O)-, -NH-C(O)-(C 1 -C 22 ) Alkylene-C(O)-NH-, -NH-(C 1 -C 22 Alkilen-OP(O) 2 O-, -NH-(C 1 -C 22 )Alkylene-CH((C 1 -C 22 )alkylene-OH)-OP(O) 2 O-, -NH-(C 1 -C 22 )Alkylene-CH((C 1 -C 22 )alkylene-OH)-(C 1 -C 22 Alkilen-OP(O) 2 O-, -C(O)-NH-(C 1 -C 22 )Alkylene-NH-C(O)-, -(C 1 -C 22 Alkilen-OP(O) 2 O-, -(C 1 -C 22 )Alkilen-OP(O)O-, -(C 1 -C 22 )Alkilen-OP(O)(S)O-, -(C 1 -C 22 )Alkylene-OS(O)2-O-, -(C 1 -C 22 )alkylene-S(O)2-O-, -(C 1 -C 22 ) Alkilen-S(O)-O-, -OP(O) 2 -O-(C 1 -C 22 Alkilen-OP(O) 2 O-, -OP(O)-O-(C 1 -C 22 )Alkilen-OP(O)O-, -OP(O)(S)O-(C 1 -C 22 )Alkilen-OP(O)(S)O-, -OS(O) 2 -O-(C 1 -C 22 Alkilen-OS(O) 2 -O-, -S(O) 2 -O-(C 1 -C 22 ) Alkylene-S(O) 2 -O- and -OS(O)-(C 1 -C 22 ) Linked to an oligonucleotide via at least one binding site selected from the group consisting of alkylene-S(O)-O-; and Oligonucleotides are oligonucleotide delivery agents selected from the group consisting of antisense oligonucleotides (ASOs), antisense RNAs, short interfering RNAs (siRNAs), microRNAs (miRNAs), small activating RNAs (saRNAs), double-stranded RNAs (dsRNAs), and small guide RNAs (sgRNAs).

13. The oligonucleotide delivery agent according to claim 12, wherein the oligonucleotide comprises at least a portion of the sequences described in SEQ ID NOs: 1 to 53.

14. The following formula AA 【Chemistry 27】 Formula AA (Here, the delivery-enhancing compound (DEC) portion is derived from an oligonucleotide delivery-enhancing compound according to any one of claims 1 to 9 and is directly or indirectly linked to at least one oligonucleotide.) An oligonucleotide delivery agent comprising a structure represented by, The DEC is bonded to the oligonucleotide via at least one first binding portion, The TM is connected to the DEC via at least one second coupling portion, Each of the first and second bonding regions is independently selected from the following group: direct bond, -O-, -S-, -C(O)-, -NH-, -N((C 1 -C 12 )alkyl)-, -N((C 1 -C 12 )alkyl)-C(O)-O-, -OC(O)-, -C(O)-O-, -OC(O)-O-, -C(O)-NH-, -OP(O) 2 O-, -OP(O)O-, -OP(O)(S)O-, -OS(O) 2 -O-, -S(O) 2 -O-, -S(O)-O-, -(C 1 -C 22 )Alkilen-, -(C 1 -C 22 ) Alkylene-NH-, -NH-(C 1 -C 22 )Alkilen-, -(C 1 -C 22 )Alkylene-NH-C(O)-, -(C 1 -C 22 ) Alkylene-C(O)-, -(C 1 -C 22 ) Alkylene-C(O)-O-, -C(O)-(C 1 -C 22 )Alkylene-, -NH-C(O)-(C 1 -C 22 )alkylene-, -C(O)-NH-(C 1 -C 22 )Alkylene-, -C(O)-(C 1 -C 22 ) Alkylene-NH-, -NH-(C 1 -C 22 ) Alkylene-C(O)-, -C(O)-(C 1 -C 22 ) Alkylene-C(O)-, -NH-(C 1 -C 22 )alkylene-NH-, -C(O)-(C 1 -C 22 ) Alkylene-C(O)O-, -OC(O)-(C 1 -C 22 ) Alkylene-C(O)-O-, -C(O)-O-(C 1 -C 22 ) Alkylene-OC(O)-, -C(O)-(C 1 -C 22 )Alkylene-NH-C(O)-, -NH-C(O)-(C 1 -C 22 ) Alkylene-C(O)-, -NH-C(O)-(C 1 -C 22 ) Alkylene-C(O)-NH-, -NH-(C 1 -C 22 Alkilen-OP(O) 2 O-, -NH-(C 1 -C 22 )Alkylene-CH((C 1 -C 22 )alkylene-OH)-OP(O) 2 O-, -NH-(C 1 -C 22 )Alkylene-CH((C 1 -C 22 )alkylene-OH)-(C 1 -C 22 Alkilen-OP(O) 2 O-, -C(O)-NH-(C 1 -C 22 )Alkylene-NH-C(O)-, -(C 1 -C 22 Alkilen-OP(O) 2 O-, -(C 1 -C 22 )Alkilen-OP(O)O-, -(C 1 -C 22 )Alkilen-OP(O)(S)O-, -(C 1 -C 22 Alkilen-OS(O) 2 -O-, -(C 1 -C 22 ) Alkylene-S(O) 2 -O-, -(C 1 -C 22 ) Alkilen-S(O)-O-, -OP(O) 2 -O-(C 1 -C 22 Alkilen-OP(O) 2 O-, -OP(O)-O-(C 1 -C 22 )Alkilen-OP(O)O-, -OP(O)(S)O-(C 1 -C 22 )Alkilen-OP(O)(S)O-, -OS(O) 2 -O-(C 1 -C 22 Alkilen-OS(O) 2 -O-, -S(O) 2 -O-(C 1 -C 22 ) Alkylene-S(O) 2 -O- and -OS(O)-(C 1 -C 22 ) Alkilen-S(O)-O-; Oligonucleotides are selected from the group consisting of short interfering RNA (siRNA), small activating RNA (saRNA), microRNA (miRNA), antisense oligonucleotide (ASO), and small guide RNA (sgRNA). An oligonucleotide delivery agent in which the target portion is one or more selected from the group consisting of ligands, peptides, nucleic acids, oligonucleotides, aptamers, lipids, fatty acids, low molecular weight molecules, polyethylene glycol, amino acids, cholesterol, carbohydrates, and antibodies or antibody fragments.

15. The oligonucleotide delivery agent according to claim 12, having a structure represented by any of the formulas AAI to AAXXIV. 【Chemistry 28】 【Chemistry 29】 (Here, L represents the connecting part, 【Transformation 30】 The symbol represents an oligonucleotide delivery enhancing compound. 【Chemistry 31】 This represents a double-stranded oligonucleotide in which each strand interchangeably represents either a sense strand or an antisense strand, and each end is symmetrical or asymmetrical. symbol 【Chemistry 32】 (where represents a single-stranded oligonucleotide, and each of a, b, and c is an integer from 1 to 50.)

16. The oligonucleotide delivery agent according to claim 12, wherein at least one hydrogen atom in the delivery-enhancing compound portion, binding portion, target portion and / or oligonucleotide is substituted with a deuterium atom.

17. a) The oligonucleotide delivery agent according to claim 12; and b) One or more components selected optionally from the group consisting of pharmaceutically acceptable carriers, excipients, solvents, diluents, stabilizers, dispersants, buffers, compatibilizers, preservatives, and combinations thereof. A pharmaceutical composition containing the following:

18. Use of the pharmaceutical composition according to claim 17 in the manufacture of a pharmaceutical for modulating the expression of a target gene in a subject, Here, subjects are selected from a group consisting of mammals, rodents, mice, rats, non-human primates, humans, and their cells.

19. The use according to claim 18, wherein the oligonucleotide or target gene comprises at least a portion of the sequences described in SEQ ID NOs: 1 to 53.

20. The use according to claim 18, wherein the pharmaceutical composition increases or decreases the expression of a target gene.

21. If the target gene is associated with a disease or disorder, The use according to claim 18, wherein the target gene is associated with a disease or disorder in the central nervous system (CNS), brain, spinal cord, liver, lungs, kidneys, intestines, pancreas, gallbladder, heart, lymph nodes, spleen, stomach, bladder, muscles, or bones.

22. The use according to claim 21, wherein the disease is cancer.

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