Molecular degraders for the treatment of iga nephropathy

Abstract

The present invention the invention concerns bifunctional compounds of Formula (I) A-T-L1-AG, Formula (II) A-L1-Con(L2-AG)n or Formula (III) Ak´-Th-L3 ii-AGj' wherein A is a protein that binds to the hinge region of galactose deficient IgA1 antibodies or a protein that binds to autoantibodies of galactose deficient IgA antibodies and AG is an asiaglycoprotein receptor binding moiety (ASGPR binding moiety). L1, Con and L2 are part of a linker between A and AG. The A has the ability to bind to antibodies that are a cause of IgA nephropathy and the asiaglycoprotein receptor binding moiety binds to hepatic cells thereby initiating endocytosis and removal of the antibodies that are a cause of IgA nephropathy from the blood stream.

Description

Title Molecular Degraders for the Treatment of IgA Nephropathy Description Introduction The present invention the invention concerns bifunctional compounds of Formula (I) A-T-L1-AG, Formula (II) A-L1-Con(L2-AG)nor Formula (III) Ak´-Th-L3 ii-AGj’wherein A is a protein that binds to the hinge region of galactose deficient IgA1 antibodies or a protein that binds to autoantibodies of galactose deficient IgA antibodies and AG is an asiaglycoprotein receptor binding moiety (ASGPR binding moiety). L1, Con and L2are part of a linker between A and AG. The A has the ability to bind to antibodies that are a cause of IgA nephropathy and the asiaglycoprotein receptor binding moiety binds to hepatic cells thereby initiating endocytosis and removal of the antibodies that are a cause of IgA nephropathy from the blood stream. Background of the invention IgA nephropathy (IgAN), also known as Berger's disease or synpharyngitic glomerulonephritis, is a form of inflammation of the kidney. IgA Nephropathy is a form of primary glomerulonephritis and the most common type of glomerulonephritis. The global incidence is 2.5 per 100,000 per year. Prevalence as percentage of biopsy-proven primary glomerulonephritis is about 30 % in most developed countries (see Lai et al. Nature Reviews, vol 2, 2016, pp.1-20). IgA Nephropathy results in end-stage renal disease in 30 to 40% of patients within 20 to 30 years of diagnosis. A more aggressive form exists (aggressive IgA Nephropathy or aggressive Berger’s disease), but is rare. It is on the NORD list of rare diseases. There is also evidence for familial IgA Nephropathy (about 5 to 10% of the cases), which is accompanied with poorer prognoses than for patients with sporadic disease. This also comes with a higher risk for renal failure. The direct cause for the disease is the deposition of antibody complexes in the glomerular mesangium of the kidneys, which induce proliferation of mesangial cells and increase the synthesis of the extracellular matrix. This elicits an immune response resulting in more deposits. An inflammation results. Galactose- deficient IgA1 (Gd-IgA1) has been identified as one of the most convincing key mediators in thepathogenesis of IgAN (see Yasutake et al, “Novel lectin-independent approach to detect galactose- deficient IgA1 in IgA nephropathy”, NephrolDial Transplant (2015) 30: 1315-1321). IgA1 is one of the two subclasses of the IgA antibody observed in humans. Gd-IgA1 are produced by IgA1-secreting cells (normal functioning B cells) through abnormal biosynthesis of O-glycans. At the hinge-region segment of the IgA1 heavy chain, there are nine sites for potential attachment of O-glycans, of which three to six are usually glycosylated per hinge (see Lai et al). In glycan intact (normal) IgA1 N-acetylgalactosamine (GalNAc) is attached to serine or threonine and a further molecule of galactose is bound to the N- acetylgalactosamine. Either of or both of N-acetylgalactosamine and galactose may additionally be sialylated. In Gd-IgA1 the galactose is missing at least in some positions and serine or threonine may only have N-acetylgalactosamine side-chains that may or may not be sialylated. The serum levels of Gd-IgA1 of patients with IgA nephropathy are elevated and are associated with a risk of progression to end-stage renal disease (Yasutake et al). The body develops antibodies against Gd- IgA1, either of the IgA1 type or of the IgG type. These antibodies form complexes with Gd-IgA1. The formed complexes either form in the glomerular mesangium or deposit therein or both. High levels of circulating IgA immune complexes are thought to be very common in IgA nephropathy, but the finding so far has no diagnostic use. To date no medications have been approved by the US FDA specifically for IgA nephropathy. Yasutake et al have recently developed a new method to detect Gd-IgA1. They developed a Gd-IgA1- specific monoclonal antibody “KM55” that specifically recognizes enzymatically generated Gd-IgA1 from human plasma IgA1. KM55 was obtained by using a human IgA1 hinge region peptide with the sequence H-C223PST*PPT*PS*PS*TPPT*PSPS240-NH2, with five N-acetylgalactosamine (GalNAc) residues added to the serine and threonine residues that are marked with *, as antigen. Immunization or rats with this peptide resulted in the isolation of the antibody KM55, which is specific against Gd-IgA1. The present inventors have shown that proteins including antibodies may be removed from the blood stream by use of bifunctional molecules (see WO 2019 / 199621 A1, WO 2023 / 028590 A1 and WO 2023 / 028597). These bifunctional molecules comprise a first moiety that binds to the protein to be removed and a second moiety that binds to the hepatocyte asialoglycoprotein receptor (in the following also “ASGPR”). The ASGPR is presented at the surface of liver cells and binds sugars, aminosugars and molecules that have a partial structure thereof or a similar structure. Once bound to the ASGPR the molecules are endocytosed and digested in the hepatocyte. Therefore, the bifunctional molecules are introduced into the blood stream, bind to the protein or other molecule to be removed with the firstmoiety and bind to the ASPGR by means of the second moiety. These complexes are then endocytosed and the molecules to be removed from the blood stream are digested by the hepatocytes. These bifunctional molecules therefore utilize the endolysosomal machinery in the liver to eliminate unwanted molecules as for example antibodies including autoantibodies from the blood stream. WO 2023 / 028590 A1 and WO 2023 / 028597 A1, disclose bifunctional molecules in which the first moiety binds to anti-β1ECIIautoantibodies and the second moiety to ASGPR. The first moiety binding to the anti- β1ECIIautoantibodies is in the following also designated “anti-β1adrenergic receptor antibody binding moiety” or “anti-β1AR antibody binding moiety.” It is shown in these documents that these bifunctional molecules are able to remove anti-β1ECIIautoantibodies from the blood stream and can therefore ameliorate DCM. Molecular structures that bind to ASGPR, i.e. asialoglycoprotein receptor binding moieties also named “ASGPR binding moieties” or “ASGPR targeting agents” are well known. Sugars such as galactose, n- acetyl galactosamine and other galactose derivatives are often used as ASGPR binding moieties. Such derivatives and other structural parts suitable for the aforementioned bifunctional molecules are for example disclosed in WO 2023 / 028590 A1, WO 2023 / 028597 A1, WO 2021 / 155317 A1, WO 2022 / 235699 A1 and WO 2019 / 199621 A1, M.G. Finn and V. Mascitti et al. in the Journal of the American Chemical Society, 134, 1978 (2012). EP 3145934 B1 discloses bicyclic sugar derivatives for this purpose and the literature cited therein and the literature cited during the examination thereof discloses further asialoglycoprotein receptor binding moieties. Objective of the invention It is the purpose of the present invention to provide active substances that may be useful in the prevention of the treatment of IgA nephropathy. It is a further purpose of the present invention to provide compounds that may remove Gd-IgA1 or autoantibodies thereof from the blood stream. It is especially a purpose of the present invention to provide bifunctional compounds that bind to asialoglycoprotein receptors and to Gd-IgA1 or to asialoglycoprotein receptors and autoantibodies of Gd-IgA1. Detailed descriptionIn one aspect of the present invention the invention concerns a compound of Formula (I) or Formula (II), or a pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof, having the structure of A-L1-AG Formula (I) or A-L1-Con(L2-AG)nFormula (II), wherein A is a protein that is a binding moiety and selected from the group consisting of a BM1, BM2, BM3 and BM4, wherein BM1 is a binding moiety that binds to the hinge region of galactose deficient IgA1 antibodies (GD-IgA1) and has an amino acid sequence at least 80% homologous to SEQ ID NO: 1: HMVC#LSYRGRPVC#FSL, wherein # marks a disulfide bridge between the two amino acids, BM2 is a binding moiety that binds to the hinge region of galactose deficient IgA1 antibodies and has an amino acid sequence at least 80% homologous to SEQ ID NO: 2: VDNKFNKETIQASQEIRLLPNLNGRQKLAFIHSLLDDPSQSANLLAEAKKLNDAQAPK, BM3 is a binding moiety that binds tothe Fc region of IgA1 antibodies and has an amino acid sequence at least 75% homologous to SEQ ID NO: 3: VPS-(Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-P-(Ser-Alpha-GalNAc)-P-(Ser- Alpha-GalNAc)-(Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-PSPS, wherein GalNAc refers to N-acetylgalactosamine, and BM4 is a binding moiety that binds to autoantibodies of galactose deficient IgA1 antibodies and has an amino acid sequence that differs no more than by one amino acid from SEQ ID NO: 26: Gly-Gly-PS-(Thr-Alpha-GalNAc)-PPor from SEQ ID NO: 27: PS-(Thr-Alpha-GalNAc)-PP, wherein GalNAc refers to N-acetylgalactosamine; L1and L2are linker and all linker L1and L2may be the same or different and all occurrences of L2in Formula (II) may be the same or different and L1and L2may also be a direct bond; Con is a connector that is covalently bonded to an open valence of linker L1and to an open valence of each linker L2; n is an integer of 2 or 3 and AG is an asiaglycoprotein receptor binding moiety (ASGPR binding moiety) and each occurrence of AG in Formula (II) may be the same of different. The compounds of the present invention (hereafter also “degraders”) and especially the compounds of Formulae (I) and (II) are pharmaceutically acceptable compounds. Compounds of the present invention are molecular degraders of galactose deficient IgA1 antibodies or of autoantibodies of galactose deficient IgA1 antibodies. The moiety A binds to galactose deficient IgA1 antibodies or to auto- antibodies of galactose deficient IgA1 antibodies and the moiety AG binds to the hepatocyte asialoglycoprotein receptor. The complexes of the compounds of the present invention and the IgA1 antibodies or autoantibodies of IgA1 antibodies are then endocytosed and digested by the hepatocytes, thereby eliminating the galactose deficient IgA1 antibodies or autoantibodies of galactose deficient IgA1 antibodies from the blood stream. BM1 and BM2 bind to galactose deficient IgA1 antibodies. BM1 binds specifically to its hinge region and BM2 binds to the Fc region thereof. BM3 and BM4 bind to autoantibodies of galactose deficient IgA1 antibodies. Removing galactose deficient IgA1 antibodies and / or autoantibodies of galactose deficient IgA1 antibodies reduces or prevents formation of antibody complexes comprising these antibodies in the blood stream or in the glomerular mesangium of the kidneys. The compounds of the present invention therefore remove or prevent formation of these antibody complexes in the glomerular mesangium, which cause IgA nephropathy. In various aspects, compounds of the present invention are useful in methods of preventing, treating, and / or ameliorating IgA nephropathy in a subject when administered in therapeutically effective amounts. The compounds of the present invention are therefore suitable for the treatment or prevention of IgA nephropathy.In a further embodiment of the present invention, the present disclosure is directed to compounds of Formula (III): Ak´-L3ii-AGj’,Formula (III) or a pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof. These compounds of the present invention are also useful for removing circulating proteins which are associated with a disease state or condition in a patient or subject as described herein. In the compound of Formula (III), A is as defined herein and L3is a linker. In the compound of Formula (III): L3is a chemical moiety having a valency from 1 to 15 which covalently attaches to one or more A and / or AG group; k’ is an integer from 1 to 15; h is an integer from 1 to 15; ii is an integer from 0 to 15; j’ is an integer from 1 to 15. In various embodiments, L3has a valency of 1 to 10. In various embodiments, L3has a valency of 1 to 5. In various embodiments, L3has a valency of 2, 3 or 4. In various embodiments, in the compound of Formula (III), L3is selected from the group consisting of L1and -L1-Con(L2-)n. In various embodiments, in the compound of Formula (III), L3comprises a partial structure selected from the group consisting of L1, L2, -Con(-)n, -L1-Con(-)n, -Con(L2-)n, -L1-Con(L2-)n, LinkerA, LinkerB, LinkerC, LinkerD, and / or combinations thereof as described herein. L3may comprise one or more of each L1, L2or -L1-Con(L2-)n of Formulae (I) or (II). L1and / or L2may also consist of a combination of one or more LinkerAand one or more LinkerBas described hereunder. The group -L1-Con(L2-)nof Formula (II) may be identical to LinkerCand / or LinkerDas described hereunder. The group -L1-Con(L2-)nof Formula (II) may be identical to a combination of one or more of LinkerAand / or LinkerBwith one or more of either LinkerCor LinkerD. -L1-Con(L2-)n of Formula (II) may also include LinkerA, LinkerB, LinkerCand / or LinkerDas described hereunder.In the following formula the designations “Extracellular Targeting Ligand” and “Extracellular Protein Targeting Ligand” refers to the group A- of Formulae (I) and / or (II) and to the group A- of Formula (III). Binding moiety A (peptide) The amino acid sequence A provides the binding properties to the compounds of the present invention (degraders) for binding to galactose deficient IgA1 antibodies or to autoantibodies thereof. Since both, galactose deficient IgA1 antibodies and their autoantibodies are pathogens that play a crucial role in the development of IgA nephropathy, removal of either of them or both is beneficial in preventing, treating and / or ameliorating of IgA nephropathy. A is a peptide selected from the group consisting of BM1, BM2, BM3 and BM4. Peptides of the type BM1 and BM2 are homologues of KM55, a known Gd-IgA1-specific monoclonal antibody that specifically recognizes enzymatically generated Gd- IgA1 from human plasma IgA1 and therefore have an affinity towards Gd-IgA1 antibodies, more specifically their hinge region. They may be used to remove Gd-IgA1 antibodies from circulation. Peptides of the types BM3 and BM4 are mimetics of the hinge region of Gd-IgA1 antibodies and have an affinity towards autoantibodies of Gd-IgA1 antibodies. They may be used to remove autoantibodies of Gd-IgA1 antibodies from circulation. All four types, BM1, BM2, BM3 and BM4 are beneficial in preventing, treating and / or ameliorating of IgA nephropathy. BM1 is a binding moiety that binds to the hinge region of galactose deficient IgA1 antibodies and has an amino acid sequence at least 80% homologous to SEQ ID NO: 1: HMVC#LSYRGRPVC#FSL, wherein # marks a disulfide bridge, BM2 is a binding moiety that binds to the hinge region of galactose deficient IgA1 antibodies and has an amino acid sequence at least 80% homologous to SEQ ID NO: 2: VDNKFNKETIQASQEIRLLPNLNGRQKLAFIHSLLDDPSQSANLLAEAKKLNDAQAPK BM3 is a binding moiety that binds to the Fc region of IgA1 antibodies and has an amino acid sequence at least 75% homologous to SEQ ID NO: 3: VPS-(Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-P-(Ser-Alpha-GalNAc)-P-(Ser- Alpha-GalNAc)-(Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-PSPS,wherein GalNAc refers to N-acetylgalactosamine, and BM4 is a binding moiety that binds to autoantibodies of galactose deficient IgA1 antibodies and has an amino acid sequence that differs no more than by one amino acid from SEQ ID NO: 26 Gly-Gly-PS-(Thr-Alpha-GalNAc)-PP or from SEQ ID NO: 27: PS-(Thr-Alpha-GalNAc)-PP, wherein GalNAc refers to N-acetylgalactosamine. BM1 Preferably the bisulfide bridge is retained in all amino acid sequences of BM1. In one embodiment BM1 is at least 90% homologous to SEQ ID NO: 1. Amino acids added or introduced by way of substitution include synthetically modified amino acids and D-amino acids. BM1 preferably is selected from the group comprising SEQ ID NO: 1 and amino acid sequences that differ from SEQ ID NO: 1 at least in that one or more amino acids of SEQ ID NO: 1 are substituted by a non-standard amino acid selected from the group consisting of D-amino acids, N-methylated amino acids, S-penicillamine, L-thiazolidine-4- carboxylic acid, sarcosine, L-pipecolic acid and norleucine. BM1 more preferably is selected from the group comprising SEQ ID NO: 1 and amino acid sequences that differ from SEQ ID NO: 1 only in that one or more amino acids of SEQ ID NO: 1 are substituted by a non-standard amino acid selected from the group consisting of D-amino acids, N-methylated amino acids, S-penicillamine, L-thiazolidine-4- carboxylic acid, sarcosine, L-pipecolic acid and norleucine. Even more preferably BM1 is selected from the group comprising SEQ ID NO: 1 and amino acid sequences that differ from SEQ ID NO: 1 at least in that or only in that in that one or more amino acids of SEQ ID NO: 1 are substituted by a non-standard amino acid selected from the group consisting of the amino acids in Table (A): Table (A)N-methylated amino acids are preferred. In a more preferred embodiment the non-standard amino acids are selected from the groups consisting of S-penicillamine, N-methyl leucine, N-methyl arginine, N- methyl methionine, N-methyl serine, 3-hexyl alanine and D-histidine. In an even more preferred embodiment of the present invention, BM1 is selected from the group consisting of SEQ ID NO: 1 and amino acid sequences that differ from SEQ ID NO: 1 only in that one or more amino acids of SEQ ID NO: 1 are substituted as described in the following Table (B): Table (B):In an even more preferred embodiment, BM1 is SEQ ID NO: 1 or BM1 is an amino acid sequence that differs from SEQ ID NO: 1 in that only one of the amino acids of SEQ ID NO: 1 is changed, e.g. exactly one amino acid is deleted, added or substituted for another amino acid. Preferably BM1 is SEQ ID NO: 1 or BM1 is an amino acid sequence that differs from SEQ ID NO: 1 in that exactly one amino acid is substituted for another amino acid and more preferably that the amino acid introduced is an amino acid of Table (A) and even more preferably one amino acid is substituted as disclosed in Table (B). In afurther preferred embodiment the cysteine closer to the N-terminal end of SEQ ID NO: 1 is not substituted by S-penicillamine. Most preferred one amino acid is substituted as disclosed in Table (B) and the amino acid introduced is selected from the group consisting of N-methyl leucine, N-methyl arginine and N-methyl methionine. BM1 may be selected from the following amino acid sequences: SEQ ID NO: 1: HMVC#LSYRGRPVC#FSL (see e.g. BH3656) SEQ ID NO: 4: HMVC#LSYRGRPVC#FS(N-Me-Leu) (see e.g. BH3740), SEQ ID NO: 5: HMVC#LSYRGRPVC#F(N-Me-Ser)L (see e.g. BH3737), SEQ ID NO: 6: H(N-Me-Met)VC#LSYRGRPVC#FSL (see e.g. BH3735), SEQ ID NO: 7: HMVC#LSYRGRPVPen#FSL (see e.g. BH3776), SEQ ID NO: 8: hMVC#LSYRGRPVC#FSL (see e.g. BH3736), SEQ ID NO: 9: HMVC#LSYRGRPVC#[Hex]SL (see e.g. BH3777), SEQ ID NO: 10: HMVC#LSY(N-Me-Arg)GRPVC#FSL (see e.g. BH3707), SEQ ID NO: 11: HMVC#LSYRGrPVC#FSL (see e.g. BH3658), SEQ ID NO: 12: HMVC#LSYRGRPVC#FSk (see e.g. BH3739), SEQ ID NO: 13 HMVPen#LSYRGRPVPen#FSL (see e.g. BH3708), SEQ ID NO: 14 HMVPen#LSYRGRPVC#FSL (see e.g. BH3738), SEQ ID NO: 15 HQVC#LSYRGRPVC#FST (see e.g. BH3708), SEQ ID NO: 16 VPen#LSYRGrPVPen#FS(N-Me-Leu) (see e.g. BH3778), SEQ ID NO: 17 VPen#LSYRGrPVPen#FSl (see e.g. BH3744), SEQ ID NO: 18 VC#LSYRGRVC#FSL (see e.g. BH3709), SEQ ID NO: 20 VPen#LSYRGrPVPen#FSk (see e.g. BH3745), SEQ ID NO: 21 VPen#LSYRGrPVPen#FSL (see e.g. BH3742), SEQ ID NO: 22 VPen#LSYRGrPVPen#F (see e.g. BH3743), SEQ ID NO: 23: HMVC#LSYRGRPvC#FSL (see e.g. BH3741), wherein # marks a disulfide bridge between the two amino acids. BM1 is preferably an amino acid sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO: 14. More preferably BM1 is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO: 10. Even more preferably BM1 is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO: 7. Most preferably BM1 is SEQ ID NO: 4.BM2 The peptide sequences of BM2 bind to the Fc region of IgA antibodies. They are not specific for galactose-deficient IgA antibodies. They also bind to native (normal) IgA antibodies. Compounds of the present invention that comprise peptide sequences of the type BM2 make use of the fact that IgA antibodies are present in excess in the human body. They are not needed in the amount present. The total human IgA antibodies in humans comprise about 1 to 3 % galactose-deficient IgA. Application of the compounds of the type BM2 will remove galactose-deficient IgA antibodies and native IgA antibodies alike. A reduction of the concentration of native IgA antibodies is not harmful for the patient, but the reduction of the amount of galactose deficient IgA will be beneficial in preventing, treating and / or ameliorating IgA nephropathy. Amino acid sequences of BM2 include amino acid sequences that are arrived at by deletion of amino acids of SEQ ID NO: 2, addition of amino acids to SEQ ID NO: 2 or substitution of amino acids of SEQ ID NO: 2 with other amino acids. In one embodiment BM2 is at least 90% homologous to SEQ ID NO: 2. Amino acids added or introduced by way of substitution include synthetically modified amino acids. BM2 preferably is SEQ ID NO: 2 or comprises N-methylated amino acids or other non-standard amino acids selected from the group consisting of the amino acids in Table (A) above. N-methylated amino acids are preferred. In a more preferred embodiment the non-standard amino acids are selected from the groups consisting of S-penicillamine, N-methyl leucine, N-methyl arginine, N-methyl methionine, N- methyl serine and 3-hexyl alanine. In an even more preferred embodiment of the present invention, BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one or more amino acids of SEQ ID NO: 2 are substituted as described in Table (B) above, preferably with the proviso that BM2 does not comprise S-penicillamine and does not comprise N-methyl methionine. In an even more preferred embodiment of the present invention, BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one or more amino acids of SEQ ID NO: 2 are substituted as described in Table (B) above, with the proviso that BM2 does not comprise S-penicillamine and does not comprise N-methyl methionine. In an even more preferred embodiment of the present invention, BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one, two or three amino acids of SEQ ID NO: 2 are substituted as described in Table (B) above,preferably with the proviso that BM2 does not comprise S-penicillamine and does not comprise N- methyl methionine. Most preferably BM2 is SEQ ID NO: 2. BM3 Amino acid sequences of BM3 include amino acid sequences that are arrived at by deletion of amino acids of SEQ ID NO: 3, addition of amino acids to SEQ ID NO: 3 or substitution of amino acids of SEQ ID NO: 3 with other amino acids. In this regard, substituting an amino acid by the same amino acid that has a different O-glycan side chain as for example described in Table (C) is considered a substitution of an amino acid. In one embodiment BM3 is at least 90% homologous to SEQ ID NO: 3. Amino acids added or introduced by way of substitution include synthetically modified amino acids, preferably amino acids of Table (A). More preferably, the amino acid sequence is only altered by changing the O-glycans. In an even more preferred embodiment BM3 is selected from the group consisting of SEQ ID NO: 3 and amino acid sequences that differ from SEQ ID NO: 3 only in that one or more amino acids of SEQ ID NO: 3 are substituted as described in Table (C). In an even more preferred embodiment BM3 is selected from the group consisting of SEQ ID NO: 3 and amino acid sequences that differ from SEQ ID NO: 3 only in that one amino acid is substituted as described in Table (C): Table (C):BM3 is preferably selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 19, wherein SEQ ID NO: 19 is: SEQ ID NO: 19 VPST*PPT*PS*PS*TPPT*PSPS, wherein * marks an amino acid that bears an alpha-N-acetylgalactosamine O-glycan. Most preferably BM3 is SEQ ID NO: 3.The amino acid Ser-Alpha-GalNAc has the structure:In the amino acid sequences disclosed herein, Ser-Alpha-GalNAc may also be designated “S*” and Thr- Alpha-GalNAc may be designated “T*,” as shown above in SEQ ID NO: 16. SEQ ID NO: 3 may be written as above: “VPS-(Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-P-(Ser-Alpha-GalNAc)-P-(Ser-Alpha-GalNAc)- (Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-PSPS” or in short form as “VPST*PPT*PS*PS*T*PPT*PSPS,” wherein * marks an amino acid that bears an alpha-N-acetylgalactosamine O-glycan. BM4 Amino acid sequences of BM4 include amino acid sequences that are arrived at by deletion of one amino acid of SEQ ID NO: 26 or SEQ ID NO: 27, addition of one amino acid to SEQ ID NO: 26 or SEQ ID NO: 27 or substitution of one amino acid of SEQ ID NO: 26 or SEQ ID NO: 27 with another amino acid. In this regard, substituting an amino acid by the same amino acid that has an O-glycan side chain as forexample described in Table (C) is considered a substitution of an amino acid. Amino acids added or introduced by way of substitution include synthetically modified amino acids. Suitable examples for such synthetically modified amino acids can be found in Table (A). BM4 preferably is selected from the group consisting of SEQ ID NO: 26 and SEQ ID NO: 27 and amino acid sequences that differ from SEQ ID NO: 26 or SEQ ID NO: 27 in that only one amino acid of SEQ ID NO: 26 or SEQ ID NO: 27 is substituted. In a more preferred embodiment BM4 is selected from SEQ ID NO: 26, SEQ ID NO: 27 and sequences that differ from SEQ ID NO: 26 or SEQ ID NO: 27 only in that serine is substituted for ser-Alpha-GalNAc or Thr-Alpha-GalNAc is substituted for tyrosine. BM4 is even more preferably selected from SEQ ID NO: 26 and SEQ ID NO: 27 and most preferably is SEQ ID NO: 27. BM5 In one embodiment of the present invention, A of the compounds of the present invention (degraders) is a binding moiety BM5. BM5 is a binding moiety that binds to autoantibodies of galactose deficient IgA1 antibodies and has an amino acid sequence at least 80% homologous to SEQ ID NO: 25: SEQ ID NO: 25: HYTNPSQDVTVPSPVPSTPPTP-(Ser-Alpha-GalNAc)-PSTPPTPSPSSSHPR. Amino acid sequences of BM5 include amino acid sequences that are arrived at by deletion of amino acids of SEQ ID NO: 25, addition of amino acids to SEQ ID NO: 21 or substitution of amino acids of SEQ ID NO: 25 with other amino acids. In this regard, substituting an amino acid by the same amino acid that has a different O-glycan side chain as for described in Table (C) is considered a substitution of an amino acid. Also the substitution of serine or threonine, respectively for ser-Beta-GalNAc or thr-Beta-GalNAc is considered a substitution of an amino acid. In addition, substituting the ser-Alpha-GalNAc glycan of SEQ ID NO: 25 for serine or ser-Beta-GalNAc is likewise considered a substitution of an amino acid. In one embodiment BM5 is at least 90% homologous to SEQ ID NO: 25 and preferably BM5 is at least 95% homologous to SEQ ID NO: 25. Even more preferably BM5 differs from SEQ ID NO: 25 only in one amino acid. Amino acids added or introduced by way of substitution include synthetically modified amino acids. Examples for suitable synthetically modified amino acids can be found in Table (A).More preferably, the amino acid sequence is only altered by changing the O-glycans. In an even more preferred embodiment BM5 is selected from the group consisting of SEQ ID NO: 25 and amino acid sequences that differ from SEQ ID NO: 25 only by a substitution selected from the group consisting of (1) one or more serine of SEQ ID NO: 25 is substituted for ser-Alpha-GalNAc or ser-Beta-GalNAc, (2) one or more threonine of SEQ ID NO: 25 is substituted for thr-Alpha-GalNAc or thr-Beta-GalNAc and (3) ser- Alpha-GalNAc is substituted for serine or ser-Beta-GalNAc. Most preferably BM5 is selected from the group consisting of SEQ ID NO: 25 and amino acid sequences that differ from SEQ ID NO: 25 only by a substitution selected from the group consisting of (1) one or more serine of SEQ ID NO: 25 is substituted for ser-Alpha-GalNAc, (2) one or more threonine of SEQ ID NO: 25 is substituted for thr-Alpha-GalNAc and (3) ser-Alpha-GalNAc is substituted for serine or ser-Beta-GalNAc. BM5 is preferably selected from the group consisting of SEQ ID NO: 24 and SEQ ID NO: 25, wherein SEQ ID NO: 24 is: SEQ ID NO: 24 HYTNPSQDVTVPSPVPSTPPTP-(Ser-Beta-GalNAc)-PSTPPTPSPSSSHPR, Most preferably BM5 is SEQ ID NO: 25. A list of all peptide sequences disclosed herein can be found in the experimental part after the synthetic examples under the caption “List of peptide sequences.” In the compounds of the present invention group A is bound to linker L1by its terminal NH2 group or by its terminal COOH group. Preferably group A is bound to linker L1by its terminal NH2group. If bound by its terminal NH2group, the NH2group may have the form L1-NH-, i.e. one hydrogen atom is substituted by the linker L1. If bound by its terminal COOH group, it may have the form –CO-L1or -COO-L1, i.e. either the hydrogen or the OH group of the terminal COOH group may be substituted by L1. The terminal COOH group may also be converted to an amide group. In this case the terminal COOH group may have the form –CO-NH-L1, i.e. the hydroxyl group is substituted for a L1-NH- group. If group A is bound to linker L1by its terminal NH2 group, the C-terminal end of A is preferably a –CONH2 group, i.e. the COOH group of the terminal amino acid is converted to its amid –CONH2. In preferred embodiments of the present invention, group A is bound to linker L1by its terminal NH2group by substitution of one hydrogen atom of the NH2group by linker L1and the COOH group of the C-terminal amino acid of group A is converted to its amid –CONH2.xx% homologous means that sequences are comprised, which have a nucleic acid sequence which differs due to at least one substitution, deletion, insertion and / or addition from the indicated sequence. The term "at least one", as used herein means one, or more than one, such as "at least two", "at least three", etc... The degree of homology expressed as "% homologous" between two biological sequences, preferably proteins in the context of the present invention, can be determined by algorithms well known in the art. Preferably, the degree of homology is determined by comparing two optimally aligned sequences over a comparison window, where the fragment of sequence in the comparison window may comprise additions or deletions (e.g., gaps or overhangs) as compared to the sequence it is compared to for optimal alignment. The percentage is calculated by determining, preferably over the whole length of the polypeptide, the number of positions at which the identical residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence homology. Optimal alignment of sequences for comparison may be conducted by the local homology algorithm of Smith and Waterman (1981), by the homology alignment algorithm of Needleman and Wunsch (1970), by the search for similarity method of Pearson and Lipman (1988), by computerized implementations of these algorithms (GAP, BESTFIT, BLAST, PASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group (GCG), 575 Science Dr., Madison, WI), or by visual inspection. Given that two sequences have been identified for comparison, GAP and BESTFIT are preferably employed to determine their optimal alignment and, thus, the degree of homology. Preferably, the default values of 5.00 for gap weight and 0.30 for gap weight length are used. Groups AG In principle the asialoglycoprotein receptors (ASGPR) bind asiaglycoprotein and glycoproteins from which a sialic acid has been removed to expose galactose. The asialoglycoprotein receptors of the liver are however not very specific and bind a wide variety of molecules that comprise structures or partial structures of sugars and related molecules. The asiaglycoprotein receptor binding moiety AG of the compounds of the present invention may therefore be chosen from a wide variety of compounds. Asiaglycoprotein receptor binding moiety have been intensively researched and disclosed. Some examples are described in: WO 2023 / 028590 A1, WO 2023 / 028597 A1, WO 2021 / 155317 A1, WO2022 / 235699 A1, WO 2019 / 199621 A1, EP 3145934 B1, Reshitko, G. S., et al., “Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor,” Bioconjugate Chem, doi: 10.1021 / acs.bioconjchem.0c00202; Majouga, A. G., et al., “Identification of Novel Small- Molecule ASGP-R Ligands,” Current Drug Delivery, 2016, 13, 1303-1312, doi: 10.2174 / 1567201813666160719144651; Olshanova, A. S., et al., “Synthesis of a new betulinic acid glycoconjugate with N-acetyl-D-galactosamine for the targeted delivery to hepatocellular carcinoma cells,” Russian Chemical Bulletin, International Edition, Vol. 69, No. 1, pp. 158—163, January 2020; Yamansarov, E. Yu., et al., “New ASGPR-targeted ligands based on glycoconjugated natural triterpenoids,” Russian Chemical Bulletin, International Edition, Vol. 68, No. 12, pp. 2331—2338, December 2019; Congdon, M. D., et al., “Enhanced Binding and Reduced Immunogenicity of Glycoconjugates Prepared via Solid-State Photoactivation of Aliphatic Diazirine Carbohydrates,” Bioconjugate Chem, doi: 10.1021 / acs.bioconjchem.0c00555; and Dhawan, V., et al., “Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment,” Carbohydrate Research 509 (2021) 108417, doi: 10.1016 / j.carres.2021.108417. AG of the present invention may be any known asiaglycoprotein receptor binding moiety and may especially be any asiaglycoprotein receptor binding moiety disclosed in the aforementioned publications. The following ASGPR binding moieties are illustrative and not intended to be limiting. Preferably AG is selected from the group consisting of monosaccharides, disaccharides, oligosaccharides of up to 20 monosaccharides and derivatives thereof. The monosaccharides are preferably selected from the group consisting of aldoses, aldotetroses, aldopentoses, aldohexoses, ketotrioses, ketotetroses, ketopentose, ketohexoses, aminosugars, sulfosugars, sedoheptulose and sedoheptulose anhydride. The disaccharides are preferably selected from the group consisting of sucrose, lactose, maltose, trehalose, cellobiose, kojibiose, nigerose, isomaltose, β,β-trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiluose, mannobiose, melibiose, melibiulose, rutinose, rutinulose and xylobiose. Even more preferred, the group AG of the compounds of the present invention is selected from the group consisting of galactose, talose and their derivatives. In a most preferred embodiment AG is galactose or a derivative thereof. Galactose has the structureand talose has the structureAs can be seen talose is the C2epimer of galactose and therefore only differs in the stereochemistry at C2. Galactose and talose chelate with the asialoglycoprotein receptors of the liver by means of the oxygen atoms bonded to the C3and / or C4atom. It is therefore preferred that these groups are not altered in the asiaglycoprotein receptor binding moiety AG of the compounds of the present invention. All other parts of the structures may be altered to adjust the properties of the compounds of the present invention. Alteration may have an effect on the affinity of the groups to the asialoglycoprotein receptors of the liver or may influence the pharmacokinetic and / or pharmacodynamics of the compounds of the present invention. Further considerations in the choice of the structure of AG are ease of production, stability under physiological conditions, stability in hepatocytes and other factors. The most simple suitable derivatives of galactose and talose that are useful in the present invention are 1-deoxygalactose, 2-deoxygalactose, 1,2-deoxygalactose, 1-deoxytalose, 2-deoxytalose and 1,2-deoxytalose. In preferred embodiments AG is selected from the following formulae: (Galactose-based derivatives)Formula AG-3 Formula AG-4, (Talose based derivatives)Formula AG-7, Formula AG-8,Formula AG-11 and Formula AG-12 wherein T is selected from the group consisting of a direct bond and O (an oxygen atom) and U is selected from the group consisting of a direct bond, -CH2-, O (an oxygen atom) and O-CH2, wherein if U is O-CH2, the carbon atom of O-CH2is bound to the C5-atom of the sugar ring moiety and * marks the bond that bonds AG to the remainder of the compounds of the present invention, e.g. L1, L2, L3or Con, with the proviso that no oxygen-oxygen bond is formed between AG and the remainder of the compounds of the present invention. That means that T and U are not O (an oxygen atom) and U is not O-CH2, when AG is bound to an oxygen atom of the remainder of the compounds of the present invention, e.g. L1, L2, L3or Con. Some of the embodiments of L1, L2, L3and Con enclosed herein have terminal oxygen atoms or their definitions allow for terminal oxygen atoms. If an oxygen atom of AG is bound to an oxygen atom of the remainder of the compounds of the present invention a peroxide partial structure results, which is a potentially unstable. The compounds of the present invention preferably do not comprise an oxygen-oxygen bond and an oxygen atom of AG may not be bound to an oxygen atom of the remainder of the compounds of the present invention. More preferably, AG is of Formulae AG-1 to AG-5 and even more preferably of Formula AG-1, AG-2 and AG-4. Most preferably, AG is of Formula AG-5, wherein U is CH2 or U is O-CH2 and if U is O-CH2, AG is not bound to an oxygen atom of the remainder of the compounds of the present invention or AG is ofFormula AG-2, wherein U is CH2or U is O-CH2and if U is O-CH2, AG is not bound to an oxygen atom of the remainder of the compounds of the present invention. Definition of variables: Hereunder further variables used in Formulae AG-1 to AG-12 and variables used in other formulae described herein are defined. Further variables are defined in other parts of the present text. X1is 1 to 5 contiguous atoms independently selected from O, S, N(R6), and C(R4)(R4), wherein if X1is 1 atom then X1is O, S, N(R6), or C(R4)(R4), if X1is 2 atoms then no more than 1 atom of X1is O, S, or N(R6), if X1is 3, 4, or 5 atoms then no more than 2 atoms of X1are O, S, or N(R6), wherein preferably no two oxygen atoms are adjacent to each other; Unless R is defined otherwise for other embodiments herein, R is selected from the group consisting of H, or C1-C3 alkyl optionally substituted with 1-3 hydroxyl groups; R1is selected from the group consisting of hydrogen, hydroxyl, F, Cl, Br, I, -CN, -N3, alkyl optionally substituted with 1, 2, 3, or 4 substituents, C1-C6-alkyl-CN optionally substituted with 1, 2, 3, or 4 substituents, alkenyl optionally substituted with 1, 2, 3, or 4 substituents, alkynyl optionally substituted with 1, 2, 3, or 4 substituents, haloalkyl optionally substituted with 1, 2, 3, or 4 substituents, aryl optionally substituted with 1, 2, 3, or 4 substituents, arylalkyl optionally substituted with 1, 2, 3, or 4 substituents, heteroaryl optionally substituted with 1, 2, 3, or 4 substituents, heteroaryl alkyl optionally substituted with 1, 2, 3, or 4 substituents, heterocycle optionally substituted with 1, 2, 3, or 4 substituents, heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents, alkoxy optionally substituted with 1, 2, 3, or 4 substituents, haloalkoxy optionally substituted with 1, 2, 3, or 4 substituents, -O-alkenyl, -O-alkynyl, -OR6, C1-C6-alkyl-OR6, -SR6, C1-C6alkyl-SR6, -NR6R7, C0-C6alkyl-NR6R7, - C(O)R3, C0-C6alkyl-C(O)R3, -S(O)R3, C1-C6alkyl-S(O)R3, -C(S)R3, C1-C6alkyl-C(S)R3, -S(O)2R3, C1-C6alkyl-S(O)2R3, -N(R8)-C(O)R3, C1-C6alkyl-N(R8)-C(O)R3, -N(R8)-S(O)R3, C1-C6alkyl-N(R8)-S(O)R3, -N(R8)-C(S)R3, C1-C6alkyl- N(R8)-C(S)R3, -N(R8)-S(O)2R3, C1-C6alkyl-N(R8)-S(O)2R3, -O-C(O)R3, C1-C6alkyl-O-C(O)R3, -O-S(O)R3, C1- C6alkyl-O-S(O)R3, -O-C(S)R3, C1-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C1-C6alkyl-N3, -O-S(O)2R3, or C0-C6alkyl-O- S(O)2R3, each of which is optionally substituted with 1, 2, 3, or 4 substituents; In preferred embodiments R1is selected from the groups consisting from H,;wherein or the wavy line respectively mark the bond with which R2is bonded to the remainder of the compound of the present invention. In certain embodiments R1is C0-C6alkyl-cyano optionally substituted with 1, 2, 3, or 4 substituents. Most preferred R1is hydrogen. R2is selected from the group consisting of hydrogen, optionally substituted amino, alkyl optionally substituted with 1, 2, 3, or 4 substituents, alkenyl optionally substituted with 1, 2, 3, or 4 substituents, allyl optionally substituted with 1, 2, 3, or 4 substituents, alkynyl optionally substituted with 1, 2, 3, or 4 substituents, aryl optionally substituted with 1, 2, 3, or 4 substituents, a heterocycle optionally substituted with 1, 2, 3, or 4 substituents, heteroaryl containing 1, 2 or 3 heteroatoms in the ring which are independently selected from N, O, and S and wherein the heteroaryl groups are optionally substituted with 1, 2, 3, or 4 substituents, R10, alkoxy optionally substituted with 1, 2, 3, or 4 substituents, -O-alkenyl optionally substituted with 1, 2, 3, or 4 substituents, -O-alkynyl optionally substituted with 1, 2, 3, or 4 substituents, -O-aryl optionally substituted with 1, 2, 3, or 4 substituents, - O-heteroaryl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-alkyl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-alkenyl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-alkynyl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-heteroaryl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-aryl optionally substituted with 1, 2, 3, or 4 substituents, -NR8-C(O)R10, -NR8-S(O)- R3optionally substituted with 1, 2, 3, or 4 substituents, -NR8-C(S)-R3optionally substituted with 1, 2, 3, or 4 substituents, -NR8-S(O)(NR6)-R3optionally substituted with 1, 2, 3, or 4 substituents, -N=S(O)(R3)2 optionally substituted with 1, 2, 3, or 4 substituents, -NR8C(O)NR9S(O)2R3optionally substituted with 1, 2, 3, or 4 substituents, -NR8-S(O)2-R10optionally substituted with 1, 2, 3, or 4 substituents, -NR8-C(NR6)- R3optionally substituted with 1, 2, 3, or 4 substituents, alkyl-C(O)-R3, -C(O)-R3, haloalkyl, -OC(O)R3,wherein and the wavy line, respectively, mark the bond with which R2is bonded to the remainder of the compound of the present invention. R2is preferably selected from the group consisting ofwherein R is an optional substituent selected from the group consisting of H, or C1-C3 alkyl optionally substituted with 1-3 hydroxyl groups. Additionally, R2is preferably selected from the group consisting of, bicyclic heterocycle, a spirocyclic heterocycle, for example, and without limitation,,a silicon containing heterocycle, for example, and without limitation, ; wherein marks the bond with which R2is bonded to the remainder of the compound of the present invention. In certain embodiments, R2is substituted with SF5, for example, and without limitation,; wherein marks the bond with which R2is bonded to the remainder of the compound of the present invention In certain embodiments R2is substituted with a sulfoxime, for example, and without limitation,; wherein marks the bond with which R2is bonded to the remainder of the compound of the present invention In certain embodiments R1and R2form a 5 to 7 membered saturated heterocycle that comprises up to 3 heteroatoms selected from the group consisting of N, S and O and preferably the heterocycle is a 5 or 6-membered heterocycle; In certain embodiments R1and R2form a 3 to 7 membered saturated optionally substituted carbocycle. Preferably the carbocycle is a 3 to 6-membered carbocycle optionally substituted by at least one halogen atom and more preferably the carbocycle is a 3-membered carbocycle substituted by two fluorine atoms; In a certain embodiments the C4and C5atoms of Formula AG-1 to Formula AG-12 are connected to form a 5 to 7 membered saturated optionally substituted heterocycle that comprises up to 3 heteroatoms selected from the group consisting of N, S and O and preferably the heterocycle is a 5 or 6-membered heterocycle, the C6carbon atom and the oxygen atom of the sugar bonded to the C6 carbon atom of the sugar may or may not be part of that heterocycle; When R1and R2form a cycle, R1and R2are preferably selected from; wherein marks the bond with which R10is bonded to the remainder of the compound of the present invention. In various embodiments, R2is -NH-C(=O)-CH3. These embodiments are very much preferred. In a preferred embodiment R2is RR. RR iswherein RAMis H, C1-C4 alkyl optionally substituted with up to 3 halo groups and one or two hydroxyl groups, -(CH2)KCOOH, -(CH2)KC(O)O-(C1-C4 alkyl) optionally substituted with 1-3 halo groups, -O- C(O)-(C1-C4alkyl) optionally substituted with 1-3 halo groups, -C(O)-(C1-C4alkyl) optionally substituted with 1-3 halo groups, or -(CH2)K-NRN3RN4,or RR iswherein RTAis H, CN, NRN1RN2, -(CH2)KOH, -(CH2)KO(C1-C4alkyl) optionally substituted with 1-3 halo groups, C1-C4alkyl optionally substituted with 1-3 halo groups, -(CH2)KCOOH, -(CH2)KC(O)O-(C1-C4alkyl) optionally substituted with 1-3 halo groups, -O-C(O)-(C1-C4 alkyl) optionally substituted with 1-3 halo groups, or - C(O)-(C1-C4 alkyl) optionally substituted with 1-3 halo groups, or RTAis a C3-C10 aryl or a three- to ten-membered heteroaryl group containing up to 5 hetero atoms in the rings, each of the aryl or heteroaryl groups being optionally substituted with up to three CN, NRN1RN2, -(CH2)KOH, -(CH2)KO(C1-C4alkyl) optionally substituted with 1-3 halo groups, C1-C3alkyl optionally substituted with 1-3 halo groups or 1-2 hydroxy groups, -O-(C1-C3-alkyl) optionally substituted from 1-3 halo groups, -(CH2)KCOOH, -(CH2)KC(O)O-(C1-C4 alkyl) optionally substituted with 1-3 halo groups, O-C(O)-(C1-C4 alkyl) optionally substituted with 1-3 halo groups, or -(CH2)KC(O)-(C1-C4 alkyl) optionally substituted with 1-3 halo groups, or RTAis,optionally substituted with up to three C1-C3alkyl groups which are optionally substituted with up to three halo groups; or RTAiswherein the wavy line marks the bond with which RTAis bonded to the remainder of the compound of the present invention. RN, RN1, RN2, RN3, RN4are each independently H or C1-C3alkyl optionally substituted with one to three halo groups or one or two hydroxyl groups and each -(CH2)K group is optionally substituted with 1- 4 C1-C3 alkyl groups which are optionally substituted with 1-3 fluoro groups or 1-2 hydroxyl groups; IM is independently at each occurrence an integer from 0 to 6; K is independently at each occurrence an integer from 0 to 4. In one preferred embodiment R2is selected from -NR6COR3, -NR6-(5-membered heteroaryl) and- NR6-(6-membered heteroaryl), each of which R2groups is optionally substituted with 1, 2, 3 or 4 independent substituents as described herein, for example 1, 2, 3, or 4 substituents independently selected from F, Cl, Br, haloalkyl, or alkyl.R2is preferably selected fromwherein R is an optional substituent as defined herein and wherein the wavy line marks the bond with which R2is bonded to the remainder of the compound of the present invention. R3at each occurrence is independently selected from hydrogen, alkyl, heteroalkyl, haloalkyl (including -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CH2F, and -CF2CF3), arylalkyl, heteroarylalkyl, alkenyl, alkynyl, and, heteroaryl, heterocycle, -OR8, and -NR8R9; R4is independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR6, -NR6R7, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3;R5is independently selected from hydrogen, heteroalkyl,, C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, Cl, Br, I, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, -O-alkenyl, -O-alkynyl, C0-C6alkyl- OR6, C0-C6alkyl-SR6, C0- C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl- C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)- C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl- N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0- C6alkyl-O-S(O)R3, C0- C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, and C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, 3, or 4 substituents.R6and R7are independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, arylalkyl, heteroaryl alkyl, alkenyl, alkynyl, and, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R6and R7are independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, arylalkyl, heteroaryl alkyl, alkenyl, alkynyl, and, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl- NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3. R8and R9are independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocycle. R10is preferably selected from C5or C6heterocycles, bicyclic heterocycles, spirocyclic heterocycle, -NR6-heterocycle and more preferably from C5or C6heterocycles comprising 1 to 3 heteroatoms selected from N, O and S as ring atoms. In even more preferred embodiments R10is selected from, wherein marks the bond with which R10is bonded to the remainder of the compound of the present invention. R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, azide, amino, cyano, -NR6R7, -NR8SO2R3, -NR8S(O)R3, haloalkyl, heteroalkyl, and, heteroaryl, and heterocycle; R30is preferably selected from:, wherein marks the bond with which R30is bonded to the remainder of the compound of the present invention. R200is selected from,; wherein the wavy line marks the bond with which R200is bonded to the remainder of the compound of the present invention. Boc is tert.-butyloxycarbonyl. In the compounds of the present invention, tt is independently selected from 1, 2, or 3. In the compounds of the present invention, ss is 3 minus tt (3-tt). In the compounds of the present invention, xx is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25 unless stated otherwise. In the compounds of the present invention, yy is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25 unless stated otherwise. In the compounds of the present invention, zz is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25 unless stated otherwise. Aminosugars Among the derivatives of monosaccharides, disaccharides and oligosaccharides aminosugars are preferred. In a preferred embodiment AG is a monosaccharide, disaccharide, or oligosaccharide, wherein one or more of the hydroxy (OH) groups in the particular sugar is (are) replaced (independently of each other) with a -NRG2RG3 group, wherein RG2 and RG3 are each independently selected from the group consisting of hydrogen and -C(=O)R and an optionally substituted 5- or 6-membered aromatic heterocycle, wherein R is C1-10 alkyl and wherein the heterocycle or R, respectively, are optionally substituted by 1-5 groups selected from the group consisting of halogen, C1-10 alkoxy, C1-10 aminoalkyl, and combinations thereof, or RG2 and RG3 taken together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocycle that is optionally substituted by 1-5 substituents selected from the group consisting of optionally substituted C1-10 alkyl, optionallysubstituted C1-10 alkoxy, optionally substituted C1-10 aminoalkyl, optionally substituted C6-10 aryl, optionally substituted C5-10 heteroaryl, halogen, and combinations thereof. The 5- or 6-membered aromatic heterocycles of this embodiment preferably comprise one or more heteroatom as ring atom that is selected from the group consisting of N, O and S. The 5- or 6-membered aromatic heterocycles of this embodiment may be aromatic or non-aromatic and they may be saturated or unsaturated. In a preferred embodiment -NRG2RG3 is –NH-C(=O)-CH3. In a more preferred embodiment of the compounds of the present invention that comprise partial structures of aminosugars, AG has the structure, wherein T is a direct bond or O (an oxygen atom) and * marks the bond to the remainder of the compounds of the present invention with the proviso that not oxygen-oxygen bond is formed between AG and the remainder of the compounds of the present invention. In a more preferred embodiment RG2is hydrogen and RG3is an aromatic heterocycle selected from the group consisting of 1H-pyrrole, pyrazole, imidazole, furan, thiophene, oxazole, isoxazole, isothiazole, thiazole, triazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine and triazine. In an even more preferred embodiment RG2is hydrogen and RG3is -C(=O)-CH3. Accordingly, in a very preferred embodiment AG is n- acetylgalactosamine (GalNAc), which is bound by the oxygen atom of the C1 atom (i.e. T is O) to the remainder of the compounds of the present invention. For the purposes of this invention the sugar molecule or its derivative may be bonded to the remainder of the compounds of the present invention by any part of their structure. They can for example be bonded by a carbon atom or an oxygen atom of the sugar to the remainder of the compounds of the present invention. Galactose, talose and their derivatives are preferably bound by means of C1, C5or C6or by means of the oxygen atoms of the hydroxyl group of the C1or C6carbon atom thereof. The C5and C6positions are preferred. Usually the bond to the remainder of the molecule is formed by substituting one hydrogen atom or a hydroxyl group for the bond to the remainder of the molecule. When the sugar or the derivative thereof is connected through the C1position, then that carbon may be appropriately functionalized for linking, for example by substituting a hydrogen atom orthe hydroxyl group for a group selected from the groups consisting of amino, allyl, alkyne or hydroxyl- allyl group. When the sugar or the derivative thereof is connected through the C5carbon atom the C6carbon atom, i.e. the HO-C6H2- group may be substituted for the bond to the remainder of the molecule. The bond between the sugar or the derivative thereof and the remainder of the compound of the present invention may be formed by substituting the remainder of the molecule for a hydrogen atom or an OH group of the sugar. Formulae of sugar derivatives Further sugar derivatives that are useful as group AG in the present invention that are derivatives of galactose may be selected from the group consisting of:wherein these compounds are preferably bonded to the remainder of the compounds of the present invention by the C1, C5or C6carbon atom or an oxygen atom of a hydroxyl group attached thereto, by substituting the hydrogen atom of the hydroxyl group for a bond to the remainder of the compounds of the present invention, as described above. More preferably these compounds are bonded by the C5 or C6 atom or a hydroxyl group attached thereto, as described above. Further sugar derivatives that are useful as group AG in the present invention that are derivatives of talose may be selected from the group consisting of:wherein these compounds are preferably bonded to the remainder of the compounds of the present invention by the C1, C5or C6carbon atom or an oxygen atom of a hydroxyl group attached thereto, by substituting the hydrogen atom of the hydroxyl group for a bond to the remainder of the compounds of the present invention, as described above. More preferably these compounds are bonded by the C5 or C6 atom or a hydroxyl group attached thereto, as described above. These compounds can be attached to the remainder of the compounds of the present invention through any suitable reactive group contained therein. Without limitation, they can be attached to a linker or Con as described herein through or by reaction with at least one OH, NH, vinyl, alkynyl, amide,acid, ester, ketone, or aromatic halogen contained therein. Suitable reaction modes for attaching these compounds to a linker or Con as described herein include, but are not limited to, substitution (e.g. alkylation of OH or NH groups), esterification (forming an ester), amidation (forming an amide), transesterification (exchanging one ester for another), transamidation (exchanging one amide for another), azide-alkyne cycloaddition, and other reactions capable of forming C-C, N-C, or O-C bonds with vinyl and alkynyl groups such as cycloadditions, aminations, oxidations, alkylations, rearrangement reactions (e.g. Claisen, Cope, etc.), and the like. In a more preferred embodiment AG is of formula AG-4, wherein R2is -NH-R, wherein R is selected from the group consisting of acetyl which may be substituted with a group selected from the group consisting of up to three fluorine atoms; and a 5 or 6-membered single cycle aromatic heterocycle with up to three heteroatoms in the ring, that may be unsubstituted or substituted with at least one group selected from halogen and C1-C3 alkyl, which may be substituted with one or more halogen atoms, preferably fluorine. In an even more preferred embodiment R1is H and R2is selected from the group consisting of acetyl, 1,2,4-thiadiazole which is substituted by a –CF3group and 1,4-diazine. Herein, preferably the 1,2,4-thiadiazole group is connected to the -NH- of R2in 5-position of the 1,2,4- thiadiazole group. Preferably the 1,4-diazine group is connected to the -NH- of R2in 2-position of the 1,4-diazine and the –CF3 group is located in 6-position of the 1,4-diazine. Among those even more preferred are compounds of the present invention wherein AG is of formula AG-4, wherein R2is -NH-R and R is selected from the group consisting of –C(=O)-CH3, -C(=O)-CF3, -C(=O)-CH2-CH3, -C(=O)-CH(CH3)2and –C(=O)-cyclopropyl. Compounds of the present invention wherein R is -C(=O)-CH2-CH3are most preferred, i.e. compounds in which AG is of formula AG-4, wherein R2is –NH-C(=O)-CH2-CH3. Single sugar moieties In an even more preferred embodiment AG is selected from the group consisting ofAG-(xi) AG-(xii) AG-(xiii) wherein the wavy lines mark the bond by which the sugar moiety is bonded to the remainder of the compounds of the present invention. Among these AG-(i) to (AG(vii) are preferred, AG-(i), AG-(v) and AG-(vii) are more preferred and AG-(i) is most preferred. Other-Based groups AG In some embodiments, the asiaglycoprotein binding moieties can be any of the moieties described in: Reshitko, G. S., et al., “Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor,” Bioconjugate Chem, doi: 10.1021 / acs.bioconjchem.0c00202; Majouga, A. G., et al., “Identification of Novel Small-Molecule ASGP- R Ligands,” Current Drug Delivery, 2016, 13, 1303-1312, doi: 10.2174 / 1567201813666160719144651; Olshanova, A. S., et al., “Synthesis of a new betulinic acid glycoconjugate with N-acetyl-D-galactosamine for the targeted delivery to hepatocellular carcinoma cells,” Russian Chemical Bulletin, International Edition, Vol.69, No.1, pp.158—163, January 2020; Yamansarov, E. Yu., et al., “New ASGPR-targeted ligands based on glycoconjugated natural triterpenoids,” Russian Chemical Bulletin, International Edition, Vol.68, No.12, pp.2331—2338, December 2019; Congdon, M. D., et al., “Enhanced Binding and Reduced Immunogenicity of Glycoconjugates Prepared via Solid-State Photoactivation of Aliphatic Diazirine Carbohydrates,” Bioconjugate Chem, doi: 10.1021 / acs.bioconjchem.0c00555; and Dhawan, V., et al., “Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment,” Carbohydrate Research 509 (2021) 108417, doi: 10.1016 / j.carres.2021.108417. The following ASGPR binding moieties are illustrative and not intended to be limiting. 1. GalNAc-Tyrosine Based Moieties In some embodiments, the AG can be a moiety having the structure of M1, M2, M3, or M4, or a combination thereof. In the structures of M1, M2, M3, and M4, X is independently at each occurrence O, NH, or S. In various embodiments, compounds of Formula I or Formula II can have one, two, or three groups AG with the structure of M1, M2, M3, or M4.In various embodiments, AG of formulae M1 to M4 can be conjugated to any suitable Linker L1, L2, LinkerA, LinkerB, LinkerCor LinkerDas described herein and in Congdon, M. D., et al., “Enhanced Binding and Reduced Immunogenicity of Glycoconjugates Prepared via Solid-State Photoactivation of Aliphatic Diazirine Carbohydrates,” Bioconjugate Chem, doi: 10.1021 / acs.bioconjchem.0c00555. 2. Trivalent Triazole-Based Moieties In some embodiments, comprise a moiety having the structure of M5:, M5. In the structures M5, each R is independently at each occurrence R1or R2,. In the compounds of the present invention M5 the partial structure –C(=O)-NH- of M5 preferably is part of a linker L1, L2, LinkerAor LinkerBas described herein with which M5 is bound to the group A-T- of the present invention. In various embodiments, compounds of the present invention can contain a group with the structure of M5. In various embodiments, each R in M5 is R1. In various embodiments, each R in M5 is R2. In various embodiments, M5 can be conjugated / bonded to any suitable linker as described herein and in Reshitko, G. S., et al., “Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor,” Bioconjugate Chem, doi: 10.1021 / acs.bioconjchem.0c00202. 3. Galactose- and Agarose-derived Behenic Acid Ester Moieties In various embodiments, the AG can be the galactose behenic acid ester-derived moiety M7:wherein Y1is OH or NHAc. In various embodiments, the AG can be the agarose behenic acid ester-derived moiety M8:. In various embodiments, M7 and M8 can be conjugated to any suitable linker or Con as described herein and in Dhawan, V., et al., “Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment,” Carbohydrate Research 509 (2021) 108417, doi: 10.1016 / j.carres.2021.108417. 4. Other Small Molecule Asiaglycoprotein Binding Moieties A large variety of groups that bind to the asiaglycoprotein are known. Some of them are useful in the present invention. In various embodiments, the AG can be any of the compounds 2-18 below:In various embodiments, in compounds 15 and 16, R is CH2OAc, COOH, or CH2OH. Compounds 2-18 can be conjugated / bonded to any suitable linker or Con as described herein and in Majouga, A. G., et al., “Identification of Novel Small-Molecule ASGP-R Ligands,” Current Drug Delivery, 2016, 13, 1303- 1312, doi: 10.2174 / 1567201813666160719144651; Olshanova, A. S., et al., “Synthesis of a new betulinic acid glycoconjugate with N-acetyl-D-galactosamine for the targeted delivery to hepatocellular carcinoma cells,” Russian Chemical Bulletin, International Edition, Vol.69, No.1, pp.158—163, January 2020; Yamansarov, E. Yu., et al., “New ASGPR-targeted ligands based on glycoconjugated natural triterpenoids,” Russian Chemical Bulletin, International Edition, Vol.68, No.12, pp.2331—2338, December 2019. Compounds 2-18 can be attached through any suitable reactive group contained therein. Without limitation, compounds 2-13 can be attached to a linker or Con as described herein through or by reaction with at least one OH, NH, vinyl, alkynyl, amide, acid, ester, ketone, or aromatic halogen contained in compounds 2-18. Suitable reaction modes for attaching compounds 2-18 to a linker or Con as described herein include, but are not limited to, substitution (e.g. alkylation of OH or NH groups), esterification (forming an ester), amidation (forming an amide), transesterification (exchanging one ester for another), transamidation (exchanging one amide for another), azide-alkyne cycloaddition, and other reactions capable of forming C-C, N-C, or O-C bonds with vinyl and alkynyl groups such as cycloadditions, aminations, oxidations, alkylations, rearrangement reactions (e.g. Claisen, Cope, etc.), and the like. Linkers L1and L2The principal function of Linkers L1and L2and Con is to connect the two functional parts A and AG of the inventive compounds with each other. In principle any group that bonds A and AG covalently with each other and which is generally stable under physiological conditions is suitable for L1, L2and Con. Therefore, a wide variety of structures is possible for L1and L2. Suitable linkers that may be used in the present invention as for example L1, L2, L3, LinkerA, LinkerB, LinkerCand / or LinkerDare disclosed in WO 2023 / 028590 A1, WO 2023 / 028597 A1, WO 2021 / 155317 A1, WO 2022 / 235699 A1, WO 2019 / 199621A1, M.G. Finn and V. Mascitti et al. in the Journal of the American Chemical Society, 134, 1978 (2012) and EP 3145934 B1. In a preferred embodiment of the present invention L1has the structure –(XG)n–, wherein n is an integer from 1 to 105 and L2has the structure –(XG)p–, wherein p is an integer from 1 to 50; wherein each occurrence of XG is independently selected from the group consisting of –CH2-, –CH(CH2–OCH3)– ,– CH(CH2–OCH2CH3)–, -C(=O)-, -NH-, –O-, -S-, –S(=O)2-, –P(=O)2- and an optionally substituted divalent cyclic group with 3 to 20 ring atoms (in the following also “CYCLE-3-20”), with the proviso that in linker L1and L2no two oxygen atoms are adjacent to each other and L2may also be a direct bond between Con and AG. CYCLE-3-20 may also include polycyclic groups, e.g. it may be for example monocyclic, bicyclic, tricyclic or tetracyclic. CYCLE-3-20 may be selected form the groups comprising heterocycles and carbocycles and both. In a very preferred embodiment CYCLE-3-20 comprises a 1,2,3-triazole ring. Even more preferably this triazole ring is prepared by a reaction between an alkyne and an azide in a click reaction. This is for example shown in various examples of the present invention. Preferably, the ring size of all aromatic cyclic groups comprised in CYCLE-3-20 is selected from optionally substituted divalent aromatic cyclic group with 5 or 6 ring atoms. Preferably, the ring size of optionally substituted divalent non-aromatic cyclic groups comprised in CYCLE-3-20 is preferably 3 to 10 ring atoms. The optionally substituted divalent aromatic cyclic group with 5 or 6 ring atoms comprised in CYCLE-3-20 are preferably benzene or heterocycles selected from the group consisting of single cycle aromatic 5- or 6-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles, pyridines, diazines and triazines. More preferably the heterocycle is a single cycle aromatic 5-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles. Even more preferably CYCLE-3-20 is a 1,2,3- triazole ring or a group,TRIAZOLE-2 wherein * marks the open valences with which the group is bound to the remainder of the molecule (in the following this partial structure is also designated also “TRIAZOLE-2”), or a groupTRIAZOLE-3 wherein * marks the open valences with which the group is bound to the remainder of the molecule (in the following also “TRIAZOLE-3”). In any case it is very much preferred that CYCLE-3-20 comprises at least one 1,2,3-triazole ring, even more preferred a 1H-1,2,3-triazole ring. More preferably CYCLE-3-20 is a triazole and most preferably it is selected from the group consisting of a 1H-1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, TRIAZOLE-2 and TRIAZOLE-3. One benefit from the use of 1H-1,2,3- triazole rings in the linkers is ease of assembly of the compounds of the present invention. 1H-1,2,3- triazole groups can be readily prepared by click reactions between azides and alkynes. Therefore, various parts of the molecules may be synthesized and equipped with an alkyne group or an azide and the various parts may then finally bonded by means of a click reaction between azide and alkyne. Preferably no two heteroatoms selected from the group consisting of N and O are adjacent to each other. In some embodiments of the present invention the linker L1and L2do not comprise carboxyl ester groups. In a more preferred embodiment the compound of the present invention L1and L2are copolymers with a chain length of 3 to 50 atoms, comprising one or more of –(CH2)r–, wherein r is an integer in the range of 1 to 5, and one of the hydrogen atoms in each –CH2- residue may be substituted by a residue selected from the group consisting of a halogen atom or a residue –CH2-O-CH3or –CH2-O-CH2-CH3, and wherein a plurality of –(CH2)r– moieties may be bonded to each other by a residue selected from the group consisting of –O–, –CONH–, –NHCONH–, –SO2-NH– and -PO2-NH–. r is preferably an integer in the range of 1 to 4 and more preferably 1 to 3. In this embodiment L1and L2may also comprise optionally CYCLE-3-20, which may comprise at least one or consists of a substituted divalent single cycle aromatic 5-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles. Even more preferably comprises a triazole ring or is a triazole, including triazoles selected form the group of 1H-1,2,3-triazole, TRIAZOLE-2 and TRIAZOLE-3 and most preferably CYCLE-3-20 is a triazole and most preferably a 1H-1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, or TRIAZOLE-2 or TRIAZOLE-3. Even more preferred are embodiments wherein L1and L2are copolymers comprising repeating units selected from the group consisting of –CH2-, -NH-, –CH2-O-, –(CH2CH2-O)-, –(CH2-NH)-, –(CH2CH2-NH)-, -CH2C(=O)-, -CH2CH2C(=O)-, -CH2CH2CH2C(=O)-, -C(=O)CH2CH2C(=O)- and CYCLE-3-20 which comprises at least one or consists of a substituted divalent single cycle aromatic 5-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles. Even more preferably comprises a triazole ring or is a triazole, including triazoles selected form the group of 1H-1,2,3-triazole, TRIAZOLE-2 and TRIAZOLE-3 and most preferably CYCLE-3-20 is a triazole and most preferably a 1H-1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, or TRIAZOLE-2 or TRIAZOLE-3. L1and L2preferably consist of the repeating units. In preferred non-limiting embodiments L1, L2LinkerAand / or LinkerBare independently selected from:wherein: R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkylene, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, -S(O)-, -C(S)-, -C(O)NR6-, - NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnaturalamino acid, alkenylene, alkynylene, haloalkylene, alkoxyalkylene, heterocycle, heteroaryl, -[(CR3002)aa- O]aa -, -CH2CH2-[O-(CH2)2]aa-O-, -CH2CH2-[O-(CH2)2]aa-NR6-, -CH2CH2-[O- (CH2)2]aa-, -[-(CH2)2-O-]aa-, -[O- (CH2)2]aa-, -[CH2CH(CH2-OCH3)]aa-, -[CH2CH(CH2–OCH2CH3)]aa-, -[O-CH(CH3)C(O)]aa-, -[C(O)-CH(CH3)-O]aa-, - [O-CH2C(O)]aa-, -[C(O)-CH2-O]aa -, a divalent residue of a fatty acid, a divalent residue of an unsaturated or saturated mono- or di-carboxylic acid; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21and CYCLE-3-20 which comprises at least one or consists of a substituted divalent single cycle aromatic 5-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles. Even more preferably comprises a triazole ring or is a triazole, including triazoles selected form the group of 1H-1,2,3-triazole, TRIAZOLE-2 and TRIAZOLE-3 and more preferably CYCLE-3-20 is a triazole and most preferably it is selected from the group consisting of a 1H- 1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, TRIAZOLE-2 and TRIAZOLE-3; R300are independently of each other selected from the groups consisting of H and C1-C3 alkyl; aa is independently selected at each instance from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and the remaining variables are as defined herein. In the formulae of the present invention marks an open valence for bonding to the remainder of the compounds of the present invention. In one embodiment L1is a direct bond and L2isIn one embodiment L2is a direct bond and L1isIn preferred embodiments R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkylene, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, - S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnatural amino acid, alkenylene, alkynylene, haloalkylene, alkoxyalkylene, heterocycle, heteroaryl, - [(CR3002)aa-O]aa-, -CH2CH2-[O-(CH2)2]aa-O-, -CH2CH2-[O-(CH2)2]aa-NR6-, -CH2CH2-[O- (CH2)2]aa-, -[-(CH2)2-O-]aa- , -[O-(CH2)2]aa-, -[CH2CH(CH2-OCH3)]aa-, -[CH2CH(CH2–OCH2CH3)]aa-, -[O-CH(CH3)C(O)]aa-, -[C(O)-CH(CH3)- O]aa-, -[O-CH2C(O)]aa-, -[C(O)-CH2-O]aa-, a divalent residue of a fatty acid, a divalent residue of an unsaturated or saturated mono- or di-carboxylic acid and CYCLE-3-20 which comprises at least one or consists of a substituted divalent single cycle aromatic 5-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles. Even more preferably comprises a triazole ring or is a triazole, including triazoles selected form the group of 1H-1,2,3-triazole, TRIAZOLE-2 and TRIAZOLE-3 and more preferably CYCLE-3-20 is a triazole and most preferably it is selected from the group consisting of a 1H-1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, TRIAZOLE-2 and TRIAZOLE-3; R300and aa are as defined above and the remaining variables are as defined herein. In more preferred embodiments R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkylene, -C(O)-, -C(O)O-, -OC(O)-, - C(O)NR300-, -NR300C(O)-, -O-, -S-, -NR300-, -P(O)(R300)O-, -P(O)(R300)-, a divalent residue of a natural or unnatural amino acid, alkenylene, alkynylene, haloalkylene, alkoxyalkylene, -[(CR3002)aa-O]aa-, -CH2CH2- [O-(CH2)2]aa-O-, -CH2CH2-[O-(CH2)2]aa-NR6-, -CH2CH2-[O- (CH2)2]aa-, -[-(CH2)2-O-]aa-, -[O-(CH2)2]aa-, - [CH2CH(CH2-OCH3)]aa-, -[CH2CH(CH2–OCH2CH3)]aa-, -[O-CH(CH3)C(O)]aa-, -[C(O)-CH(CH3)-O]aa-, -[O- CH2C(O)]aa-, -[C(O)-CH2-O]aa-, a divalent residue of a fatty acid, a divalent residue of an unsaturated or saturated mono- or di-carboxylic acid and CYCLE-3-20 which comprises at least one or consists of a substituted divalent single cycle aromatic 5-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles. Even more preferably comprises a triazole ring or is a triazole, including triazoles selected form the group of 1H-1,2,3-triazole, TRIAZOLE-2 and TRIAZOLE-3 and more preferably CYCLE-3-20 is a triazole and most preferably it is selected from the group consisting of a 1H- 1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, TRIAZOLE-2 and TRIAZOLE-3;R300and aa are as defined above and the remaining variables are as defined herein. In a very preferred embodiment, L1and / or L2comprise groups selected from the group consisting of –O-, -CH2- and divalent triazole ring, preferably L1and / or L2comprise a triazole selected from the group consisting of a 1H-1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, TRIAZOLE-2 and TRIAZOLE-3. In one embodiment a divalent residue of an amino acid is selected from, wherein the amino acid can be oriented in either direction and wherein the amino acid can be in the L- or D-form or a mixture thereof. In one embodiment a divalent residue of a dicarboxylic acid is generated from a nucleophilic addition reaction:Non-limiting embodiments of a divalent residue of a dicarboxylic acid generated from a nucleophilic addition reaction include:wherein yy is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. In one embodiment a divalent residue of a dicarboxylic acid is generated from a condensation reaction:Non-limiting embodiments of a divalent residue of a dicarboxylic acid generated from a condensation include:wherein xx and yy are independently of each other selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. Non-limiting embodiments of a divalent residue of a saturated dicarboxylic acid include:Non-limiting embodiments of a divalent residue of a saturated dicarboxylic acid include:, wherein xx is selected from 0, 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. Non-limiting embodiments of a divalent residue of a saturated monocarboxylic acid is selected from butyric acid (-OC(O)(CH2)2CH2-), caproic acid (-OC(O)(CH2)4CH2-), caprylic acid (-OC(O)(CH2)5CH2-), capric acid (-OC(O)(CH2)8CH2-), lauric acid (-OC(O)(CH2)10CH2-), myristic acid (-OC(O)(CH2)12CH2-), pentadecanoic acid (-OC(O)(CH2)13CH2-), palmitic acid (-OC(O)(CH2)14CH2-), stearic acid (- OC(O)(CH2)16CH2-), behenic acid (-OC(O)(CH2)20CH2-), and lignoceric acid (-OC(O)(CH2)22CH2-); Non-limiting embodiments of a divalent residue of a fatty acid include residues selected from linoleic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, gadoleic acid, nervonic acid, myristoleic acid, and erucic acid:Non-limiting embodiments of a divalent residue of a fatty acid is selected from linoleic acid (- C(O)(CH2)7(CH)2CH2(CH)2(CH2)4CH2-), docosahexaenoic acid (-C(O)(CH2)2(CHCHCH2)6CH2-), eicosapentaenoic acid (-C(O)(CH2)3(CHCHCH2)5CH2-), alpha-linolenic acid (-C(O)(CH2)7(CHCHCH2)3CH2-), stearidonic acid (-C(O)(CH2)4(CHCHCH2)4CH2-), y-linolenic acid (-C(O)(CH2)4(CHCHCH2)3(CH2)3CH2-), arachidonic acid (-C(O)(CH2)3,(CHCHCH2)4(CH2)4CH2-), docosatetraenoic acid (-C(O)(CH2)5(CHCHCH2)4(CH2)4CH2-), palmitoleic acid (-C(O)(CH2)7CHCH(CH2)5CH2-), vaccenic acid (-C(O)(CH2)9CHCH(CH2)5CH2-), paullinic acid (-C(O)(CH2)11CHCH(CH2)5CH2-), oleic acid (-C(O)(CH2)7CHCH(CH2)7CH2-), elaidic acid (-C(O)(CH2)7CHCH(CH2)7CH2-), gondoic acid (-C(O)(CH2)9CHCH(CH2)7CH2-), gadoleic acid (- C(O)(CH2)7CHCH(CH2)9CH2-), nervonic acid (-C(O)(CH2)13CHCH(CH2)3CH2-), mead acid (- C(O)(CH2)3(CHCHCH2)3(CH2)6CH2-), myristoleic acid (-C(O)(CH2)7CHCH(CH2)3CH2-), and erucic acid (-C(O)(CH2)11CHCH(CH2)7CH2-). In preferred embodiments L1, L2, LinkerAand / or LinkerBare independently selected from the group consisting of, -O-(CH2)3-, -NH-(CH2CH2O)3-CH2-, and =N*(C=O)(CH2)2C(=O)NHCH2CH2-(OCH2CH2)4-, wherein =N* is a ring nitrogen in a heterocyclic ring system. In a more preferred embodiment L2are independently selected from the group consisting of:,-O-(CH2)3-, -NH-(CH2CH2O)3-CH2-, and =N*(C=O)(CH2)2C(=O)NHCH2CH2-(OCH2CH2)4-, wherein =N* is a ring nitrogen in a heterocyclic ring system. In this embodiment AG is preferably an aminosugar. In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:wherein each heteroaryl, heterocycle, cycloalkyl, and aryl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, and, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:wherein each heteroaryl, heterocycle, cycloalkyl and aryl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:wherein each alkyl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:wherein each alkyl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments of the present invention L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments of the present invention L1and / or L2are independently of each other is selected from:In certain embodiments of the present invention L1and / or L2are independently of each other selected from:. In certain embodiments of the present invention L1, L2, LinkerAand / or LinkerBare independently of each other is selected from:In certain embodiments of the present invention L1, L2, LinkerAand / or LinkerBare independently of each other selected from:Į In certain embodiments L1and / or L2are independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments, L1, L2, LinkerAand / or LinkerBare independently of each other selected fromwherein each is optionally substituted with 1, 2, 3, or 4 substituents selected from R21. In certain embodiments, L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments, L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments, L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selectedfromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected fromIn certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerAand / or LinkerBare independently of each other selected from:In certain embodiments L1, L2, LinkerA, LinkerBand / or LinkerB-LinkerAare independently of each other selected from:In certain embodiments L1, L2, LinkerA, LinkerBand / or LinkerB-LinkerAare independently of each other selected from:In certain embodiments L1, L2, LinkerA, LinkerBand / or LinkerB-LinkerAare independently of each other selected from:Linker -L1-Con(L2-)n In certain embodiments -L1-Con(L2-)n is selected from:wherein: R22is independently at each occurrence selected from the group consisting of alkyl, heteroalkyl,alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which has three valences bonded to R13and R14, respectively, and is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;and the remaining variables are as defined herein. In certain embodiments -L1-Con(L2-)n is selected from:wherein: R32is independently at each occurrence selected from the group consisting of alkyl, heteroalkyl, , , alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which has three valences bonded to R13and R14, respectively, and is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; X- is an anionic group, for example Br- or Cl-;and all other variables are as defined herein. In certain embodiments L1, L2, LinkerA, LinkerB, LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:wherein tt is independently selected from 1, 2, or 3 and ss is 3 minus tt (3-tt). When tt is 1, the structures are embodiments of L1and L2, LinkerAor LinkerB. Otherwise they are embodiments of LinkerC, LinkerDor -L1-Con(L2-)n. The same is applicable to the following embodiments. In certain embodiments L1, L2, LinkerA, LinkerB, LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:wherein tt and ss are as defined herein. In certain embodiments L1, L2, LinkerA, LinkerB, LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:wherein each heteroaryl, heterocycle, cycloalkyl, and aryl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence and the alkyl substituents of the heteroaryl, heterocycle, cycloalkyl, and aryl may optionally be substituted by halogen, preferably by F; and tt and ss are as defined herein. In certain embodiments L1, L2, LinkerA, LinkerB, LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:wherein each alkyl, heteroaryl, heterocycle, cycloalkyl, and aryl can optionally be substituted with 1, 23, or 4 of any combination of halogen, alkyl, haloalkyl, and, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence and the alkyl substituents of the heteroaryl, heterocycle, cycloalkyl, and aryl may optionally be substituted by halogen, preferably by F; and tt and ss are as defined herein. In certain embodiments L1, L2, LinkerA, LinkerB, LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:wherein each alkyl, heteroaryl and aryl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence; and tt and ss are as defined herein. In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:. In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from: wherein each is optionally substituted with 1, 2, 3, or 4 substituents substituent selected from R21. In certain embodiments -L1-Con(L2-)nis selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected from:wherein each is optionally substituted with 1, 2, 3, or 4 substituents are selected from R21. In certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected fromIn certain embodiments LinkerC, LinkerDand / or -L1-Con(L2-)n, respectively, are selected fromIn various embodiments, L1, L2, LinkerA, LinkerB, LinkerCand / or LinkerDare cyclic or acyclic moieties, and may be selected from the group consisting of: a)wherein: R51is H or C1-C3 alkyl; and n'' is independently an integer ranging from 0 to 20; orb)wherein xx is as defined herein; or c)wherein: Z and Z’ are each independently a bond, -(CH2)i-O-, -(CH2)i-S-, -(CH2)i-N(R)-,, each R52is independently H or C1-C3 alkyl; each Y is independently a bond, O, S, or N-R; wherein R is H, or C1-C3 alkyl optionally substituted with 1-3 hydroxyl groups each i is independently an integer from 0 to 100; D isor a bond, with the proviso that Z, Z', and D are not each simultaneously bonds;i is as defined above j is an integer from 1 to 100; m' is an integer from 1 to 100; mm is an integer from 1 to 100; X10is O, S, or N-R; y is as defined above; R is H, or C1-C3alkyl optionally substituted with 1-3 hydroxyl groups; or d) C6-18 aryl, C3-18 heterocyclyl, C6-18 biaryl, or C6-18 heterobiaryl, each of which is optionally substituted by 1-6 substituents selected from the group consisting of F, Cl, Br, I, -ORG, -OC(O)N(RG)2, - CN, -NO, -NO2, -ONO2, -CF3, -OCF3, -RG, -N(RG)2, -SRG, -SORG, -SO2RG, -SO2N(RG)2, and -SO3RG, wherein each occurrence of RG is independently H, optionally substituted C1-10 alkyl, optionally substituted C3- 10 cycloalkyl, optionally substituted C6-18 aryl, or optionally substituted C5-18 heteroaryl. L1, L2, LinkerA, LinkerB, LinkerCand / or LinkerDmay also be combinations of the groups a) through d). Con The structural element Con of the compounds of the present invention serves as a branching point to connect one anti-β1 adrenergic receptor antibody binding moiety A with two or three asiaglycoprotein receptor binding moieties. The requirements for Con are therefore that it can form 1 covalent bond with L1or A and two or three covalent bonds with L2or AG wherein the covalent bonds are stable under physiological conditions. Con is preferably selected from the group consisting of alkyl, heteroalkyl, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which has three or more, preferably three or four valences bonded to L1, L2, A and / or AG, respectively, and is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;wherein X- is a pharmaceutically acceptable anionic group, for example Br- or Cl-; J is a direct bond or a hydrocarbon with 1 to 10 carbon atoms, preferably –(CH2)e-, wherein e is 1 to 10, more preferably 2 to 5 and all other variables are as defined herein. Preferably, R6, R7and R21of Con are hydrogen or C1-C3 alkyl. In a preferred embodiment Con is a hydrocarbon with 1 to 10 carbon atoms or a heterocycle with 4 to 8 ring members, wherein the heterocycle may be saturated or unsaturated, aromatic or aliphatic and comprise up to 4 heteroatoms as ring atoms, wherein the heteroatoms are selected from the group consisting of nitrogen, oxygen and sulfur and wherein in the hydrocarbon or the heterocycle one hydrogen atom is substituted by linker L1or by the group A-T- and n hydrogen atoms are substituted by linker L2or by the group AG. The heterocycle may further be substituted as permissible by valence with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl. Preferably Con is a hydrocarbon with 1 to 10 carbon atoms or a heterocycle with 5 to 7 ring members, wherein the heterocycle may be saturated or unsaturated, aromatic or aliphatic and comprise up to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In one embodiment Con is selected from the group consisting of, wherein RCON1and RCON2are each independently H, methyl or a bond (for attachment to another moiety) and one or more further linkers, A or AG may be bonded to these groups Con by substituting one or more hydrogen atoms. In another preferred embodiment Con iswherein 1CON, 2CON and 3CON are selected from the groups consisting of H and -(CH2)f-, with f is an integer from 1 to 10, preferably one to 5 and most preferably 1 to 3, with the proviso that at least two of 1CON, 2CON and 3CON are not hydrogen In one embodiment Con is. In an even more preferred embodiments Con is selected from the group consisting of -CH(3- n)(CH2-)n, wherein n is 2 or 3 and diazacycloheptane. It is most preferred that Con is -CH(3-n)(CH2-)n. In a preferred embodiment or the present invention one terminal end of L1is a –NH- residue, by which it is connected to Con and the one terminal end of the n L2linker are –O- residues, by which the linkers L2 are connected to Con. It is further noted that any connector or linker described herein may be connected to the remainder of the molecule of the compounds of the present invention at positions which are represented as being linked to another group using the symbol * or the symbol. Where that symbol is not used, the linker may be at one or more positions of a moiety where a hydrogen atom is located and can be substituted for a bond. General structures of Formulae (I), (II) and (III) In one embodiment, the compounds of Formulae (I), (II) or (III) have one of the following structures, wherein the designation “ASGPR Ligand” refers to the group AG and the designation “Extracellular Protein Targeting Ligand” refers to the partial structure “A-T-” of Formulae (I), (II) and (III) and LinkerA, LinkerB, LinkerCand LinkerDare as defined herein:. A. Galactose-Based ASGPR-Binding Cellular Receptor Binding Moieties AG In the following formulae examples of the structures of Formulae (I), (II) and (III) are disclosed in which AG is a galactose derivative. The partial structures of galactose and its derivatives in these formulae may be used as group AG in any of Formulae (I), (II) and (III). The partial structure marked as “Extracellular Protein Targeting Ligand” is as defined above. LinkerA, LinkerB, LinkerCand LinkerDare as defined herein. In certain embodiments, the compounds of Formulae (I) or (III) are selected from:. In various embodiments, AG is derived from the partial structure,then non-limiting examples compounds of Formulae (I) and (III) include:or the bi- or tri- substituted versions thereof or pharmaceutically acceptable salts thereof, where the bi- or tri- substitution refers to the number additional galactose derivatives attached to a linker moiety, i.e. n in Formula (II). In certain embodiments, the compounds of Formulae (I) or (III) are selected from:In certain embodiments, the compounds of Formulae (II) or (III) are selected from:In certain embodiments, the compounds of Formulae (II) or (III) are selected from:. B. Talose-Based ASGPR-Binding Cellular Receptor Binding Moieties AG In the following formulae examples of the structures of Formulae (I), (II) and (III) are disclosed in which AG is a talose derivative. The partial structures of talose and its derivatives in these formulae may be used as group AG in any of Formulae (I), (II) and (III). The definitions of variables are as described herein and especially as described above for the galactose based embodiments. In certain embodiments, the compounds of Formulae (I), (II) or (III) are selected from:In various embodiments, AG is derived from the partial structureThen non- limiting examples of AG of compounds of Formulae (I), (II) or (III) include:In some embodiments the compounds of the present invention are selected from:wherein in certain embodiments R2is selected from -NR6COR3, -NR6-(5-membered heteroaryl), and-NR6-(6-membered heteroaryl), each of which R2groups is optionally substituted with 1, 2, 3, or 4 independent, substituents as described herein, for example 1, 2, 3, or 4 substituents independently selected from F, Cl, Br, haloalkyl, or alkyl.In certain embodiments, the compounds of Formulae (II) or (III) are selected from:In certain embodiments, the compounds of Formulae (I), (II) or (III) are selected from:wherein in certain embodiments R2is selected from -NR6COR10, -NR6-(5-membered heteroaryl), and-NR6-(6-membered heteroaryl), each of which R2groups is optionally substituted with 1, 2, 3, or 4 independent, substituents as described herein, for example 1, 2, 3, or 4 substituents independently selected from F, Cl, Br, haloalkyl, or alkyl. In certain embodiments, the compounds of Formulae (I), (II) or (III) are selected from:In certain embodiments, the compounds of Formulae (I), (II) or (III) are selected from:In certain embodiments, the compounds of Formulae (II) or (III) are selected from:C. The ASGPR Ligand / Binding Moiety in Compounds of Formula II In a preferred embodiment the compounds of the present invention have a structure selected from the group consisting of:wherein L1 comprises or consists of a group -ZB-NH-, wherein the NH group is bonded to the tertiary carbon atom marked with * and R2is RR; ZB is absent, (CH2)IM, C(O)-(CH2)IM-, or C(O)-(CH2)IM-NRM-; IM is as defined above; RM is H or a C1-C3 alkyl group optionally substituted with one or two hydroxyl groups. Further groups -T-L1-Con(L2-AG)n In a preferred embodiment the compounds of Formula (II) or (III) are of Formula (II), wherein -L1- Con(L2-AG)nhas the structure:, wherein RG1'isAG is an aminosaccharide; each occurrence of XG is independently selected from the group consisting of -CH2-, -C(=O)-, - NH-, and -O-;each occurrence of ZG is independently selected from the group consisting of -CH2-, -C(=O)-, - NH-, and -O-; m is an integer from 2 to 10; n is an integer from 1 to 100; and p is an integer from 1 to 50. In a more preferred embodiment (ZG)phas the structure:. Definition L1 and L2 L1or L2or both may comprise one or more units selected from the group consisting of -(CH2CH2-O)q-, -(CH2CH(CH2OCH3)-O)q- and -(CH2CH(CH2OCH2CH3)-O)q-, wherein the values of q are independently of each other selected from an integer in the range of 1 to 10, preferably 1 to 4. In a preferred embodiment L1or L2or both comprises one or more units selected from the group consisting of - (CH2CH2-O)q-, CYCLE-3-20 which includes at least one 1,2,3-triazole ring, -CH2- and –O-, -C(=O)-, -C(=O)- O- and –C(=O)-NR-, wherein the values of q are independently of each other selected from an integer in the range of 1 to 10, preferably 1 to 4 and R is selected from the group consisting of hydrogen and C1 to C10 alkyl, preferably selected from the group consisting of hydrogen and C1-C4 alkyl and most preferably is H and wherein the triazole preferably a 1H-1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position, TRIAZOLE-2 or TRIAZOLE-3. In a more preferred embodiment L1or L2or both consist of one or more units selected from the group consisting of - (CH2CH2-O)q-, CYCLE-3-20 which includes at least one 1,2,3-triazole ring, -CH2- and –O-, -C(=O)-, -C(=O)- O- and –C(=O)-NR-, wherein the values of q are independently of each other selected from an integer in the range of 1 to 10, preferably 1 to 4 and R is selected from the group consisting of hydrogen and C1 to C10 alkyl, preferably selected from the group consisting of hydrogen and C1-C4 alkyl and most preferably is H. In an even more preferred embodiment L1or L2or both comprises one or more units selected from the group consisting of -(CH2CH2-O)q-, 1H-1,2,3-triazole, TRIAZOLE-2, TRIAZOLE-3, -CH2- and –O-, -C(=O)-, -C(=O)-O- and –C(=O)-NH-, wherein the values of q are independently of each other selected from an integer in the range of 1 to 10, preferably 1 to 4, where in the 1H-1,2,3-triazole is bound to the remainder of the molecule in 1- and 4-position. L1or L2or both may also consist of thesegroups. In a most preferred embodiment L1or L2or both consist of one or more units selected from the group consisting of -(CH2CH2-O)q-, 1H-1,2,3-triazole, TRIAZOLE-2, TRIAZOLE-3, -CH2- and –O-, -C(=O)- and –C(=O)-NH-, wherein the values of q are independently of each other selected from an integer in the range of 1 to 10, preferably 1 to 4, wherein the 1H-1,2,3-triazole is bound to the remainder of the molecule in 1- and 4-position.In even more preferred embodiments of the present invention at least one of L1and L2is selected from the group consisting of (1): -C(=O)CH2CH2C(=O)-NH-(CH2CH2-O)3-CH2CH2C(=O)-NH-CH2C(=O)-NH-, (2): –CH2-O-CH2CH2-O-CH2CH2C(=O)-NH-CH2C(=O)-NH-, (3): –CH2-O-(CH2CH2-O)3-CH2CH2C(=O)-NH-CH2C(=O)-NH-, (4): -CH2CH2CH2C(=O)-NHCH2C(O)-NH-, (5): –CH2-O-(CH2CH2-O)3-, (6): –NH-C(=O)-CH2-O-CH2CH2-O-CH2C(=O)-NH-, (7):(10):(17):or L2is a direct bond. Preferably these linkers are bound to a carbon atom of A, Con and / or AG. In even more preferred embodiments L1is selected from the group consisting of linkers (1) to (18). Embodiments of the present invention in which L1is selected from the group consisting of linkers (1) to (18) and wherein L2is selected from the group consisting of linkers (19), (20) and a direct bond are most preferred. Linkers (19) and (20) are preferably bonded to AG via the oxygen atom of the terminal –CH2- CH2-O- group. Combinations of L1 and L2 with A and / or AG Protein not specified (Formula (I) In preferred compounds of Formula (I), the L1is selected from linkers (1) to (20) and a direct bond and AG is selected from the group consisting of AG-(i) to AG-(vii).In more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (1) to (18) and AG is selected from the group consisting of AG-(i) to AG-(vii). In even more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (16) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG-(vii) and even more preferred AG is AG-(i). (ii) Formula (II) In preferred compounds of Formula (II), the L1and L2are selected from linkers (1) to (20) and a direct bond, Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii). In more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (18), L2is selected from the group consisting of linkers (19) and (20), Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii). In even more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (15), , L2is selected from the group consisting of linkers (19) and (20), Con is -CH(CH2-)3 and AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG- (vii) and even more preferred AG is AG-(i). Protein is BM1 (iii) Formula (I) In preferred compounds of Formula (I), the L1is selected from linkers (1) to (20) and a direct bond and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM1 and BM1 is selected from the group comprising SEQ ID NO: 1 and amino acid sequences that differ from SEQ ID NO: 1 only in that one or more amino acids of SEQ ID NO: 1 are substituted as described in Table (B). In more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (1) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii) and A is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO: 10. In even more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (16) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG-(vii) and even more preferred AG is AG-(i) and A is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO: 7.In most preferred compounds of Formula (I) L1is selected from the group consisting of linkers (16) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG- (v) and AG-(vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 4. (In preferred compounds of Formula (II), the L1and L2are selected from linkers (1) to (20) and a direct bond, Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii) , A is BM1 and BM1 is selected from the group comprising SEQ ID NO: 1 and amino acid sequences that differ from SEQ ID NO: 1 only in that one or more amino acids of SEQ ID NO: 1 are substituted as described in Table (B). In more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (18), L2is selected from the group consisting of linkers (19) and (20), Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii) and A is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO: 10. In even more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (15), , L2is selected from the group consisting of linkers (19) and (20), Con is -CH(CH2-)3 and AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG- (vii) and even more preferred AG is AG-(i) and A is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO: 7. In most preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (15), L2is selected from the group consisting of linkers (19) and (20), Con is -CH(CH2-)3and AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG-(vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 4. Protein is BM2 (v) Formula (I) In preferred compounds of Formula (I), the L1is selected from linkers (1) to (20) and a direct bond and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM2 and BM2 is selected from the group consisting of SEQ ID NO: 2 and an amino acid sequences that differ from SEQ ID NO: 2 only in that one or more amino acids of SEQ ID NO: 2 are substituted as described in Table (B), preferably with the proviso that BM2 does not comprise S-penicillamine and does not comprise N-methyl methionine.In more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (1) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM2 and BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one or more amino acids of SEQ ID NO: 2 are substituted as described in Table (B), with the proviso that BM2 does not comprise S-penicillamine and does not comprise N-methyl methionine. In even more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (1) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM2 and BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one, two or three amino acids of SEQ ID NO: 2 are substituted as described in Table (B), with the proviso that BM2 does not comprise S-penicillamine and does not comprise N-methyl methionine. In most preferred compounds of Formula (I) L1is selected from the group consisting of linkers (16) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG- (v) and AG-(vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 2. (vi) Formula (II) In preferred compounds of Formula (II), the L1and L2are selected from linkers (1) to (20) and a direct bond, Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM2 and BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one or more amino acids of SEQ ID NO: 2 are substituted as described in Table (B), preferably with the proviso that BM2 does not comprise S- penicillamine and does not comprise N-methyl methionine. In more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (18), L2is selected from the group consisting of linkers (19) and (20), Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM2 and BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one or more amino acids of SEQ ID NO: 2 are substituted as described in Table (B), with the proviso that BM2 does not comprise S-penicillamine and does not comprise N-methyl methionine. In even more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (15), L2is selected from the group consisting of linkers (19) and (20), Con is -CH(CH2-)3 and AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG- (vii) and even more preferred AG is AG-(i), A is BM2 and BM2 is selected from the group consisting ofSEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one, two or three amino acids of SEQ ID NO: 2 are substituted as described in Table (B), with the proviso that BM2 does not comprise S-penicillamine and does not comprise N-methyl methionine. In most preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (15), , L2is selected from the group consisting of linkers (19) and (20), Con is -CH(CH2-)3and AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG- (vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 2. Protein is BM3 (vii) Formula (I) In preferred compounds of Formula (I), the L1is selected from linkers (1) to (20) and a direct bond and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM3 and BM3 is selected from the group consisting of SEQ ID NO: 3 and amino acid sequences that differ from SEQ ID NO: 3 only in that one or more amino acid of SEQ ID NO: 3 is substituted as described in Table (C). In more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (1) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM3 and BM3 is selected from the group consisting of SEQ ID NO: 3 and amino acid sequences that differ from SEQ ID NO: 3 only in that one amino acid is substituted as described in Table (C). In most preferred compounds of Formula (I) L1is selected from the group consisting of linkers (16) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG- (v) and AG-(vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 3. (viii) Formula (II) In preferred compounds of Formula (II), the L1and L2are selected from linkers (1) to (20) and a direct bond, Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii) , A is BM3 and BM3 is selected from the group consisting of SEQ ID NO: 3 and amino acid sequences that differ from SEQ ID NO: 3 only in that one or more amino acid of SEQ ID NO: 3 is substituted as described in Table (C). In more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (18), L2is selected from the group consisting of linkers (19) and (20), Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM3 and BM3 is selectedfrom the group consisting of SEQ ID NO: 3 and amino acid sequences that differ from SEQ ID NO: 3 only in that one amino acid is substituted as described in Table (C). In most preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (15), , L2is selected from the group consisting of linkers (19) and (20), Con is -CH(CH2-)3 and AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG- (vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 3. Protein is BM4 (ix) Formula (I) In preferred compounds of Formula (I), the L1is selected from linkers (1) to (20) and a direct bond and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM4 and BM4 is selected from the group consisting of SEQ ID NO: 26 and SEQ ID NO: 27 and amino acid sequences that differ from SEQ ID NO: 26 or SEQ ID NO: 27 only in that one or more amino acid of SEQ ID NO: 3 is substituted as described in Table (C). In more preferred compounds of Formula (I) L1is selected from the group consisting of linkers (1) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM4 and BM4 is selected from the group consisting of SEQ ID NO: 26 or SEQ ID NO: 27 and amino acid sequences that differ from SEQ ID NO: 26 or SEQ ID NO: 27 only in that one amino acid is substituted as described in Table (C). In most preferred compounds of Formula (I) L1is selected from the group consisting of linkers (16) to (18), AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG- (v) and AG-(vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 27. (x) Formula (II) In preferred compounds of Formula (II), the L1and L2are selected from linkers (1) to (20) and a direct bond, Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii) , A is BM4 and BM4 is selected from the group consisting of SEQ ID NO: 26 or SEQ ID NO: 27 and amino acid sequences that differ from SEQ ID NO: 26 or SEQ ID NO: 27 only in that one or more amino acid of SEQ ID NO: 26 or SEQ ID NO: 27 is substituted. In more preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (18), L2is selected from the group consisting of linkers (19) and (20), Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3, and AG is selected from the group consisting of AG-(i) to AG-(vii), A is BM4 and BM4 is selectedfrom the group consisting of SEQ ID NO: 26 or SEQ ID NO: 27 and amino acid sequences that differ from SEQ ID NO: 26 or SEQ ID NO: 27 only in that one amino acid is substituted as described in Table (C). In most preferred compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (15), , L2is selected from the group consisting of linkers (19) and (20), Con is -CH(CH2-)3 and AG is selected from the group consisting of AG-(i) to AG-(vii), preferably consisting of AG-(i), AG-(v) and AG- (vii) and even more preferred AG is AG-(i) and A is SEQ ID NO: 27. In a more preferred embodiment of compounds of Formula (II) L1is selected from the group consisting of linkers (1) to (18), and L2is selected from the group consisting of linkers (19) and (20) and a direct bond, Con if present is selected from -CH(3-n)(CH2-)n, wherein n is 2 or 3 Single compounds In a preferred embodiment the compounds of the present invention are selected from the group consisting of:In a more preferred embodiment the compounds of the present invention are selected from the group consisting of:Most preferred are BH3407, BH3408, BH3409, BH3596, BH3740, BH3596, BH3903 and BH3923. Compounds of the present invention with a higher ASGPR Endocytosis MFI value as disclosed in the examples are generally more preferred than compounds with a lower value. Various other properties of the compounds The compounds described herein can possess one or more stereocenters, and each stereocenter can exist independently in either the (R) or (S) configuration. In certain embodiments, compounds described herein are present in optically active or racemic forms. It is to be understood that the compounds described herein encompass racemic, optically-active, regioisomeric and stereoisomeric forms, or combinations thereof that possess the therapeutically useful properties described herein. Preparation of optically active forms is achieved in any suitable manner, including by way of non-limiting example, by resolution of the racemic form with recrystallization techniques, synthesis from optically- active starting materials, chiral synthesis, or chromatographic separation using a chiral stationary phase.In certain embodiments, a mixture of one or more isomer is utilized as the therapeutic compound described herein. In other embodiments, compounds described herein contain one or more chiral centers. These compounds are prepared by any means, including stereoselective synthesis, enantioselective synthesis and / or separation of a mixture of enantiomers and / or diastereomers. Resolution of compounds and isomers thereof is achieved by any means including, by way of non- limiting example, chemical processes, enzymatic processes, fractional crystallization, distillation, and chromatography. The methods and formulations described herein include the use of N-oxides (if appropriate), crystalline forms (also known as polymorphs), solvates, amorphous phases, and / or pharmaceutically acceptable salts of compounds having the structure of any compound(s) described herein, as well as metabolites and active metabolites of these compounds having the same type of activity. Solvates include water, ether (e.g., tetrahydrofuran, methyl tert-butyl ether) or alcohol (e.g., ethanol) solvates, acetates and the like. In certain embodiments, the compounds described herein exist in solvated forms with pharmaceutically acceptable solvents such as water, and ethanol. In other embodiments, the compounds described herein exist in unsolvated form. In certain embodiments, the compound(s) described herein can exist as tautomers. All tautomers are included within the scope of the compounds presented herein. In certain embodiments, compounds described herein are prepared as prodrugs. A "prodrug" refers to an agent that is converted into the parent drug in vivo. In certain embodiments, upon in vivo administration, a prodrug is chemically converted to the biologically, pharmaceutically or therapeutically active form of the compound. In other embodiments, a prodrug is enzymatically metabolized by one or more steps or processes to the biologically, pharmaceutically or therapeutically active form of the compound. In certain embodiments, sites on, for example, the aromatic ring portion of compound(s) described herein are susceptible to various metabolic reactions. Incorporation of appropriate substituents on the aromatic ring structures may reduce, minimize or eliminate this metabolic pathway. In certain embodiments, the appropriate substituent to decrease or eliminate the susceptibility of the aromatic ring to metabolic reactions is, by way of example only, a deuterium, a halogen, or an alkyl group. Compounds described herein also include isotopically-labeled compounds wherein one or more atoms is replaced by an atom having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes suitable forinclusion in the compounds described herein include and are not limited to2H,3H,11C,13C,14C,36Cl,18F,123I,125I,13N,15N,15O,17O,18O,32P, and35S. In certain embodiments, isotopically-labeled compounds are useful in drug and / or substrate tissue distribution studies. In other embodiments, substitution with heavier isotopes such as deuterium affords greater metabolic stability (for example, increased in vivo half-life or reduced dosage requirements). In yet other embodiments, substitution with positron emitting isotopes, such as11C,18F,15O and13N, is useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically-labeled compounds are prepared by any suitable method or by processes using an appropriate isotopically-labeled reagent in place of the non- labeled reagent otherwise employed. In certain embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. The compounds described herein, and other related compounds having different substituents are synthesized using techniques and materials described herein and as described, for example, in Fieser & Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989), March, Advanced Organic Chemistry 4thEd., (Wiley 1992); Carey & Sundberg, Advanced Organic Chemistry 4th Ed., Vols. A and B (Plenum 2000,2001), and Green & Wuts, Protective Groups in Organic Synthesis 3rd Ed., (Wiley 1999) (all of which are incorporated by reference for such disclosure). General methods for the preparation of compound as described herein are modified by the use of appropriate reagents and conditions, for the introduction of the various moieties found in the formula as provided herein. Compounds described herein are synthesized using any suitable procedures starting from compounds that are available from commercial sources, or are prepared using procedures described herein. In certain embodiments, reactive functional groups, such as hydroxyl, amino, imino, thio or carboxy groups, are protected in order to avoid their unwanted participation in reactions. Protecting groups are used to block some or all of the reactive moieties and prevent such groups from participating in chemical reactions until the protective group is removed. In other embodiments, each protective group is removable by a different means. Protective groups that are cleaved under totally disparate reaction conditions fulfill the requirement of differential removal.In certain embodiments, protective groups are removed by acid, base, reducing conditions (such as, for example, hydrogenolysis), and / or oxidative conditions. Groups such as trityl, dimethoxytrityl, acetal and t-butyldimethylsilyl are acid labile and are used to protect carboxy and hydroxy reactive moieties in the presence of amino groups protected with Cbz groups, which are removable by hydrogenolysis, and Fmoc groups, which are base labile. Carboxylic acid and hydroxy reactive moieties are blocked with base labile groups such as, but not limited to, methyl, ethyl, and acetyl, in the presence of amines that are blocked with acid labile groups, such as t-butyl carbamate, or with carbamates that are both acid and base stable but hydrolytically removable. In certain embodiments, carboxylic acid and hydroxy reactive moieties are blocked with hydrolytically removable protective groups such as the benzyl group, while amine groups capable of hydrogen bonding with acids are blocked with base labile groups such as Fmoc. Carboxylic acid reactive moieties are protected by conversion to simple ester compounds as exemplified herein, which include conversion to alkyl esters, or are blocked with oxidatively-removable protective groups such as 2,4-dimethoxybenzyl, while co-existing amino groups are blocked with fluoride labile silyl carbamates. Allyl blocking groups are useful in the presence of acid- and base- protecting groups since the former are stable and are subsequently removed by metal or pi-acid catalysts. For example, an allyl- blocked carboxylic acid is deprotected with a palladium-catalyzed reaction in the presence of acid labile t-butyl carbamate or base-labile acetate amine protecting groups. Yet another form of protecting group is a resin to which a compound or intermediate is attached. As long as the residue is attached to the resin, that functional group is blocked and does not react. Once released from the resin, the functional group is available to react. Typically blocking / protecting groups may be selected from:. Other protecting groups, plus a detailed description of techniques applicable to the creation of protecting groups and their removal are described in Greene & Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, NY, 1999, and Kocienski, Protective Groups, Thieme Verlag, New York, NY, 1994, which are incorporated herein by reference for such disclosure. Preferably, the compounds of the present invention do not comprise two oxygen atoms that are adjacent to each other. Definitions Throughout this document, values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement "about X to Y" has the same meaning as "about X to about Y," unless indicated otherwise. Likewise, the statement "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z," unless indicated otherwise. In this document, the terms "a," "an," or "the" are used to include one or more than one unless the context clearly dictates otherwise. The term "or" is used to refer to a nonexclusive "or" unlessotherwise indicated. The statement "at least one of A and B" or "at least one of A or B" has the same meaning as "A, B, or A and B." In addition, it is to be understood that the phraseology or terminology employed herein, and not otherwise defined, is for the purpose of description only and not of limitation. Any use of section headings is intended to aid reading of the document and is not to be interpreted as limiting; information that is relevant to a section heading may occur within or outside of that particular section. All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the methods described herein, the acts can be carried out in any order, except when a temporal or operational sequence is explicitly recited. Furthermore, specified acts can be carried out concurrently unless explicit claim language recites that they be carried out separately. For example, a claimed act of doing X and a claimed act of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process. The term "about" as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range, and includes the exact stated value or range. The term "substantially" as used herein refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. The term "substantially free of" as used herein can mean having none or having a trivial amount of, such that the amount of material present does not affect the material properties of the composition including the material, such that the composition is about 0 wt% to about 5 wt% of the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less. The term "substantially free of" can mean having a trivial amount of, such that a composition is about 0 wt% to about 5 wt% of the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less, or about 0 wt%. The wordings “peptide” and “protein” are used interchangeably herein, unless otherwise stated or unless it is obvious from the context that something else is meant. The term "organic group" as used herein refers to any carbon-containing functional group. Examples can include an oxygen-containing group such as an alkoxy group, aryloxy group, aralkyloxy group, oxo(carbonyl) group; a carboxyl group including a carboxylic acid, carboxylate, and a carboxylate ester; a sulfur-containing group such as an alkyl and aryl sulfide group; and other heteroatom-containinggroups. Non-limiting examples of organic groups include OR, OOR, OC(O)N(R)2, CN, CF3, OCF3, R, C(O), methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, SO2R, SO2N(R)2, SO3R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)0-2N(R)C(O)R, (CH2)0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(=NH)N(R)2, C(O)N(OR)R, C(=NOR)R, and substituted or unsubstituted (C1-C100)hydrocarbyl, wherein R can be hydrogen (in examples that include other carbon atoms) or a carbon-based moiety, and wherein the carbon-based moiety can be substituted or unsubstituted. The term "substituted" as used herein in conjunction with a molecule or an organic group as defined herein refers to the state in which one or more hydrogen atoms contained therein are replaced by one or more non-hydrogen atoms. The term "functional group" or "substituent" as used herein refers to a group that can be or is substituted onto a molecule or onto an organic group. Examples of substituents or functional groups include, but are not limited to, a halogen (e.g., F, Cl, Br, and I); an oxygen atom in groups such as hydroxy groups, alkoxy groups, aryloxy groups, aralkyloxy groups, oxo(carbonyl) groups, carboxyl groups including carboxylic acids, carboxylates, and carboxylate esters; a sulfur atom in groups such as thiol groups, alkyl and aryl sulfide groups, sulfoxide groups, sulfone groups, sulfonyl groups, and sulfonamide groups; a nitrogen atom in groups such as amines, hydroxyamines, nitriles, nitro groups, N-oxides, hydrazides, azides, and enamines; and other heteroatoms in various other groups. Non-limiting examples of substituents that can be bonded to a substituted carbon (or other) atom include F, Cl, Br, I, OR, OC(O)N(R)2, CN, NO, NO2, ONO2, azido, CF3, OCF3, R, O (oxo), S (thiono), C(O), S(O), methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, SO2R, SO2N(R)2, SO3R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)0-2N(R)C(O)R, (CH2)0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(=NH)N(R)2, C(O)N(OR)R, and C(=NOR)R, wherein R can be hydrogen or a carbon-based moiety; for example, R can be hydrogen, (C1-C100)hydrocarbyl, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, or heteroarylalkyl; or wherein two R groups bonded to a nitrogen atom or to adjacent nitrogen atoms can together with the nitrogen atom or atoms form a heterocyclyl. The term "alkyl" as used herein refers to straight chain and branched alkyl groups and cycloalkyl groups having from 1 to 40 carbon atoms, 1 to about 20 carbon atoms, 1 to 12 carbons or, in some embodiments, from 1 to 8 carbon atoms. Examples of straight chain alkyl groups include those with from 1 to 8 carbon atoms such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, and n-octyl groups. Examples of branched alkyl groups include, but are not limited to, isopropyl, iso-butyl, sec- butyl, t-butyl, neopentyl, isopentyl, and 2,2-dimethylpropyl groups. As used herein, the term "alkyl" encompasses n-alkyl, isoalkyl, and anteisoalkyl groups as well as other branched chain forms of alkyl. Representative substituted alkyl groups can be substituted one or more times with any of the groups listed herein, for example, amino, hydroxy, cyano, carboxy, nitro, thio, alkoxy, and halogen groups. The term "aminoalkyl" as used herein refers to an alkyl group as defined herein wherein at least one hydrogen atom in the alkyl group is replaced by nitrogen, forming a primary, secondary, or tertiary amine, depending upon the substitution of the nitrogen. Additionally, an aminoalkyl can have one or more nitrogen atoms between any two carbons in the alkyl chain, forming a secondary or tertiary amine, depending upon the substitution of the nitrogen. The term "alkenyl" as used herein refers to straight and branched chain and cyclic alkyl groups as defined herein, except that at least one double bond exists between two carbon atoms. Thus, alkenyl groups have from 2 to 40 carbon atoms, or 2 to about 20 carbon atoms, or 2 to 12 carbon atoms or, in some embodiments, from 2 to 8 carbon atoms. Examples include, but are not limited to vinyl, - CH=C=CCH2, -CH=CH(CH3), -CH=C(CH3)2, -C(CH3)=CH2, -C(CH3)=CH(CH3), -C(CH2CH3)=CH2, cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl, and hexadienyl among others. The term "alkynyl" as used herein refers to straight and branched chain alkyl groups, except that at least one triple bond exists between two carbon atoms. Thus, alkynyl groups have from 2 to 40 carbon atoms, 2 to about 20 carbon atoms, or from 2 to 12 carbons or, in some embodiments, from 2 to 8 carbon atoms. Examples include, but are not limited to –CºCH, -CºC(CH3), - CºC(CH2CH3), -CH2CºCH, -CH2CºC(CH3), and -CH2CºC(CH2CH3) among others. The term "acyl" as used herein refers to a group containing a carbonyl moiety wherein the group is bonded via the carbonyl carbon atom. The carbonyl carbon atom is bonded to a hydrogen forming a "formyl" group or is bonded to another carbon atom, which can be part of an alkyl, aryl, aralkyl cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl group or the like. An acyl group can include 0 to about 12, 0 to about 20, or 0 to about 40 additional carbon atoms bonded to the carbonyl group. An acyl group can include double or triple bonds within the meaning herein. An acryloyl group is an example of an acyl group. An acyl group can also include heteroatoms within the meaning herein. A nicotinoyl group (pyridyl-3-carbonyl) is an example of an acyl group within the meaning herein. Other examples include acetyl, benzoyl, phenylacetyl, pyridylacetyl, cinnamoyl, and acryloyl groups and the like. When the group containing the carbon atom that is bonded to the carbonylcarbon atom contains a halogen, the group is termed a "haloacyl" group. An example is a trifluoroacetyl group. The term "cycloalkyl" as used herein refers to cyclic alkyl groups such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups. In some embodiments, the cycloalkyl group can have 3 to about 8-12 ring members, whereas in other embodiments the number of ring carbon atoms range from 3 to 4, 5, 6, or 7. Cycloalkyl groups further include polycyclic cycloalkyl groups such as, but not limited to, norbornyl, adamantyl, bornyl, camphenyl, isocamphenyl, and carenyl groups, and fused rings such as, but not limited to, decalinyl, and the like. Cycloalkyl groups also include rings that are substituted with straight or branched chain alkyl groups as defined herein. Representative substituted cycloalkyl groups can be mono-substituted or substituted more than once, such as, but not limited to, 2,2-, 2,3-, 2,4- 2,5- or 2,6-disubstituted cyclohexyl groups or mono-, di- or tri-substituted norbornyl or cycloheptyl groups, which can be substituted with, for example, amino, hydroxy, cyano, carboxy, nitro, thio, alkoxy, and halogen groups. The term "cycloalkenyl" alone or in combination denotes a cyclic alkenyl group. The term "aryl" as used herein refers to cyclic aromatic hydrocarbon groups that do not contain heteroatoms in the ring. Thus aryl groups include, but are not limited to, phenyl, azulenyl, heptalenyl, biphenyl, indacenyl, fluorenyl, phenanthrenyl, triphenylenyl, pyrenyl, naphthacenyl, chrysenyl, biphenylenyl, anthracenyl, and naphthyl groups. In some embodiments, aryl groups contain about 6 to about 14 carbons in the ring portions of the groups. Aryl groups can be unsubstituted or substituted, as defined herein. Representative substituted aryl groups can be mono-substituted or substituted more than once, such as, but not limited to, a phenyl group substituted at any one or more of 2-, 3-, 4-, 5-, or 6-positions of the phenyl ring, or a naphthyl group substituted at any one or more of 2- to 8-positions thereof. The term "aralkyl" as used herein refers to alkyl groups as defined herein in which a hydrogen or carbon bond of an alkyl group is replaced with a bond to an aryl group as defined herein. Representative aralkyl groups include benzyl and phenylethyl groups and fused (cycloalkylaryl)alkyl groups such as 4-ethyl-indanyl. Aralkenyl groups are alkenyl groups as defined herein in which a hydrogen or carbon bond of an alkyl group is replaced with a bond to an aryl group as defined herein. The term "heterocyclyl" as used herein refers to aromatic and non-aromatic ring compounds containing three or more ring members, of which one or more is a heteroatom such as, but not limited to, N, O, and S. Thus, a heterocyclyl can be a cycloheteroalkyl, or a heteroaryl, or if polycyclic, any combination thereof. In some embodiments, heterocyclyl groups include 3 to about 20 ring members,whereas other such groups have 3 to about 15 ring members. The term heterocyclyl includes rings where a CH2 group in the ring is replaced by one or more C=O groups, such as found in cyclic ketones, lactones, and lactams. Examples of heterocyclyl groups containing a C=O group include, but are not limited to, β-propiolactam, γ-butyrolactam, δ-valerolactam, and ε-caprolactam, as well as the corresponding lactones. A heterocyclyl group designated as a C2-heterocyclyl can be a 5-ring with two carbon atoms and three heteroatoms, a 6-ring with two carbon atoms and four heteroatoms and so forth. Likewise a C4-heterocyclyl can be a 5-ring with one heteroatom, a 6-ring with two heteroatoms, and so forth. The number of carbon atoms plus the number of heteroatoms equals the total number of ring atoms. A heterocyclyl ring can also include one or more double bonds. A heteroaryl ring is an embodiment of a heterocyclyl group. The phrase "heterocyclyl group" includes fused ring species including those that include fused aromatic and non-aromatic groups. For example, a dioxolanyl ring and a benzdioxolanyl ring system (methylenedioxyphenyl ring system) are both heterocyclyl groups within the meaning herein. The phrase also includes polycyclic ring systems containing a heteroatom such as, but not limited to, quinuclidyl. Heterocyclyl groups can be unsubstituted, or can be substituted as discussed herein. Heterocyclyl groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, thiophenyl, benzothiophenyl, benzofuranyl, dihydrobenzofuranyl, indolyl, dihydroindolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thianaphthalenyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl groups. Representative substituted heterocyclyl groups can be mono-substituted or substituted more than once, such as, but not limited to, piperidinyl or quinolinyl groups, which are 2-, 3-, 4-, 5-, or 6-substituted, or disubstituted with groups such as those listed herein. The term "heteroaryl" as used herein refers to aromatic ring compounds containing 5 or more ring members, of which, one or more is a heteroatom such as, but not limited to, N, O, and S; for instance, heteroaryl rings can have 5 to about 8-12 ring members. A heteroaryl group is a variety of a heterocyclyl group that possesses an aromatic electronic structure. A heteroaryl group designated as a C2-heteroaryl can be a 5-ring with two carbon atoms and three heteroatoms, a 6-ring with two carbon atoms and four heteroatoms and so forth. Likewise a C4-heteroaryl can be a 5-ring with one heteroatom, a 6-ring with two heteroatoms, and so forth. The number of carbon atoms plus the number of heteroatoms sums up to equal the total number of ring atoms. A heterocyclyl ring designated Cx-y can be any ring containing 'x' members up to 'y' members, including all intermediateintegers between 'x' and 'y' and that contains one or more heteroatoms, as defined herein. In a ring designated Cx-y, all non-heteroatom members are carbon. Heterocyclyl rings designated Cx-y can also be polycyclic ring systems, such as bicyclic or tricyclic ring systems. Heteroaryl groups include, but are not limited to, groups such as pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, thiophenyl, benzothiophenyl, benzofuranyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thianaphthalenyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl groups. Heteroaryl groups can be unsubstituted, or can be substituted with groups as is discussed herein. Representative substituted heteroaryl groups can be substituted one or more times with groups such as those listed herein. Additional examples of aryl and heteroaryl groups include but are not limited to phenyl, biphenyl, indenyl, naphthyl (1-naphthyl, 2-naphthyl), N-hydroxytetrazolyl, N-hydroxytriazolyl, N-hydroxyimidazolyl, anthracenyl (1-anthracenyl, 2-anthracenyl, 3-anthracenyl), thiophenyl (2-thienyl, 3-thienyl), furyl (2-furyl, 3-furyl) , indolyl, oxadiazolyl, isoxazolyl, quinazolinyl, fluorenyl, xanthenyl, isoindanyl, benzhydryl, acridinyl, thiazolyl, pyrrolyl (2-pyrrolyl), pyrazolyl (3-pyrazolyl), imidazolyl (1- imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl 1,2,3- triazol-4-yl, 1,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), thiazolyl (2-thiazolyl, 4- thiazolyl, 5-thiazolyl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5- pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3- pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2- quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl (2- benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl, 5-benzo[b]furanyl, 6-benzo[b]furanyl, 7- benzo[b]furanyl), 2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-benzo[b]furanyl), 3-(2,3-dihydro- benzo[b]furanyl), 4-(2,3-dihydro-benzo[b]furanyl), 5-(2,3-dihydro-benzo[b]furanyl), 6-(2,3-dihydro- benzo[b]furanyl), 7-(2,3-dihydro-benzo[b]furanyl), benzo[b]thiophenyl (2-benzo[b]thiophenyl, 3- benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5-benzo[b]thiophenyl, 6-benzo[b]thiophenyl, 7- benzo[b]thiophenyl), 2,3-dihydro-benzo[b]thiophenyl, (2-(2,3-dihydro-benzo[b]thiophenyl), 3-(2,3- dihydro-benzo[b]thiophenyl), 4-(2,3-dihydro-benzo[b]thiophenyl), 5-(2,3-dihydro-benzo[b]thiophenyl), 6-(2,3-dihydro-benzo[b]thiophenyl), 7-(2,3-dihydro-benzo[b]thiophenyl), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), indazole (1-indazolyl, 3-indazolyl, 4-indazolyl, 5- indazolyl, 6-indazolyl, 7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benzoxazolyl,2-benzoxazolyl), benzothiazolyl (1-benzothiazolyl, 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl), 5H-dibenz[b,f]azepine (5H-dibenz[b,f]azepin-1-yl, 5H-dibenz[b,f]azepine-2-yl, 5H-dibenz[b,f]azepine-3-yl, 5H-dibenz[b,f]azepine-4-yl, 5H-dibenz[b,f]azepine-5-yl), 10,11-dihydro-5H-dibenz[b,f]azepine (10,11- dihydro-5H-dibenz[b,f]azepine-1-yl, 10,11-dihydro-5H-dibenz[b,f]azepine-2-yl, 10,11-dihydro-5H- dibenz[b,f]azepine-3-yl, 10,11-dihydro-5H-dibenz[b,f]azepine-4-yl, 10,11-dihydro-5H-dibenz[b,f]azepine- 5-yl), and the like. The term "heterocyclylalkyl" as used herein refers to alkyl groups as defined herein in which a hydrogen or carbon bond of an alkyl group as defined herein is replaced with a bond to a heterocyclyl group as defined herein. Representative heterocyclyl alkyl groups include, but are not limited to, furan- 2-yl methyl, furan-3-yl methyl, pyridine-3-yl methyl, tetrahydrofuran-2-yl ethyl, and indol-2-yl propyl. The term "heteroarylalkyl" as used herein refers to alkyl groups as defined herein in which a hydrogen or carbon bond of an alkyl group is replaced with a bond to a heteroaryl group as defined herein. The term "alkoxy" as used herein refers to an oxygen atom connected to an alkyl group, including a cycloalkyl group, as are defined herein. Examples of linear alkoxy groups include but are not limited to methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and the like. Examples of branched alkoxy include but are not limited to isopropoxy, sec-butoxy, tert-butoxy, isopentyloxy, isohexyloxy, and the like. Examples of cyclic alkoxy include but are not limited to cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and the like. An alkoxy group can include about 1 to about 12, about 1 to about 20, or about 1 to about 40 carbon atoms bonded to the oxygen atom, and can further include double or triple bonds, and can also include heteroatoms. For example, an allyloxy group or a methoxyethoxy group is also an alkoxy group within the meaning herein, as is a methylenedioxy group in a context where two adjacent atoms of a structure are substituted therewith. The term "amine" as used herein refers to primary, secondary, and tertiary amines having, e.g., the formula N(group)3 wherein each group can independently be H or non-H, such as alkyl, aryl, and the like. Amines include but are not limited to R-NH2, for example, alkylamines, arylamines, alkylarylamines; R2NH wherein each R is independently selected, such as dialkylamines, diarylamines, aralkylamines, heterocyclylamines and the like; and R3N wherein each R is independently selected, such as trialkylamines, dialkylarylamines, alkyldiarylamines, triarylamines, and the like. The term "amine" also includes ammonium ions as used herein. The term "amino group" as used herein refers to a substituent of the form -NH2, -NHR, -NR2, -NR3+, wherein each R is independently selected, and protonated forms of each, except for -NR3+, which cannot be protonated. Accordingly, any compound substituted with an amino group can be viewed as an amine. An "amino group" within the meaning herein can be a primary, secondary, tertiary, or quaternary amino group. An "alkylamino" group includes a monoalkylamino, dialkylamino, and trialkylamino group. The terms "halo," "halogen," or "halide" group, as used herein, by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. The term "haloalkyl" group, as used herein, includes mono-halogen alkyl groups, poly-halogen alkyl groups wherein all halogen atoms can be the same or different, and per-halogen alkyl groups, wherein all hydrogen atoms are replaced by halogen atoms, such as fluoro. Examples of haloalkyl include trifluoromethyl, 1,1-dichloroethyl, 1,2-dichloroethyl, 1,3-dibromo-3,3-difluoropropyl, perfluorobutyl, and the like. The terms "epoxy-functional" or "epoxy-substituted" as used herein refers to a functional group in which an oxygen atom, the epoxy substituent, is directly attached to two adjacent carbon atoms of a carbon chain or ring system. Examples of epoxy-substituted functional groups include, but are not limited to, 2,3-epoxypropyl, 3,4-epoxybutyl, 4,5-epoxypentyl, 2,3-epoxypropoxy, epoxypropoxypropyl, 2-glycidoxyethyl, 3-glycidoxypropyl, 4-glycidoxybutyl, 2-(glycidoxycarbonyl)propyl, 3-(3,4- epoxycylohexyl)propyl, 2-(3,4-epoxycyclohexyl)ethyl, 2-(2,3-epoxycylopentyl)ethyl, 2-(4-methyl-3,4- epoxycyclohexyl)propyl, 2-(3,4-epoxy-3-methylcylohexyl)-2-methylethyl, and 5,6-epoxyhexyl. The term "monovalent" as used herein refers to a substituent connecting via a single bond to a substituted molecule. When a substituent is monovalent, such as, for example, F or Cl, it is bonded to the atom it is substituting by a single bond. The term “divalent” as used herein refers to a group connecting via two bonds to the remainder of the molecule it is part of. When a group is divalent, it bound to two different atoms of the remainder of the molecule. The term "hydrocarbon" or "hydrocarbyl" as used herein refers to a molecule or functional group that includes carbon and hydrogen atoms. The term can also refer to a molecule or functional group that normally includes both carbon and hydrogen atoms but wherein all the hydrogen atoms are substituted with other functional groups. As used herein, the term "hydrocarbyl" refers to a functional group derived from a straight chain, branched, or cyclic hydrocarbon, and can be alkyl, alkenyl, alkynyl, aryl, cycloalkyl, acyl, or any combination thereof. Hydrocarbyl groups can be shown as (Ca-Cb)hydrocarbyl, wherein a and b are integers and mean having any of a to b number of carbon atoms. For example, (C1-C4)hydrocarbylmeans the hydrocarbyl group can be methyl (C1), ethyl (C2), propyl (C3), or butyl (C4), and (C0- Cb)hydrocarbyl means in certain embodiments there is no hydrocarbyl group. The term "solvent" as used herein refers to a liquid that can dissolve a solid, liquid, or gas. Non- limiting examples of solvents are silicones, organic compounds, water, alcohols, ionic liquids, and supercritical fluids. The term "independently selected from" as used herein refers to referenced groups being the same, different, or a mixture thereof, unless the context clearly indicates otherwise. Thus, under this definition, the phrase "X1, X2, and X3are independently selected from noble gases" would include the scenario where, for example, X1, X2, and X3are all the same, where X1, X2, and X3are all different, where X1and X2are the same but X3is different, and other analogous permutations. The term "room temperature" as used herein refers to a temperature of about 15 °C to 28 °C. The term "standard temperature and pressure" as used herein refers to 20 °C and 101 kPa. As used herein, the term "composition" or "pharmaceutical composition" refers to a mixture of at least one compound described herein with a pharmaceutically acceptable carrier. The pharmaceutical composition facilitates administration of the compound to a patient or subject. Multiple techniques of administering a compound exist in the art including, but not limited to, intravenous, oral, aerosol, parenteral, ophthalmic, pulmonary and topical administration. A "disease" is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal's health continues to deteriorate. In contrast, a "disorder" in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal's state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal's state of health. As used herein, the terms "effective amount," "pharmaceutically effective amount" and "therapeutically effective amount" refer to a nontoxic but sufficient amount of an agent to provide the desired biological result. That result may be reduction and / or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. An appropriate therapeutic amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation. As used herein, the term "efficacy" refers to the maximal effect (Emax) achieved within an assay. As used herein, the term "pharmaceutically acceptable" refers to a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively non-toxic, i.e., the material may be administered to an individual without causing undesirable biologicaleffects or interacting in a deleterious manner with any of the components of the composition in which it is contained. As used herein, the language "pharmaceutically acceptable salt" refers to a salt of the administered compounds prepared from pharmaceutically acceptable non-toxic acids or bases, including inorganic acids or bases, organic acids or bases, solvates, hydrates, or clathrates thereof. Suitable pharmaceutically acceptable acid addition salts may be prepared from an inorganic acid or from an organic acid. Examples of inorganic acids include hydrochloric, hydrobromic, hydriodic, nitric, carbonic, sulfuric (including sulfate and hydrogen sulfate), and phosphoric acids (including hydrogen phosphate and dihydrogen phosphate). Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which include formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, malonic, saccharin, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, 4-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, trifluoromethanesulfonic, 2-hydroxyethanesulfonic, p- toluenesulfonic, sulfanilic, cyclohexylaminosulfonic, stearic, alginic, β-hydroxybutyric, salicylic, galactaric and galacturonic acid. Suitable pharmaceutically acceptable base addition salts of compounds described herein include, for example, ammonium salts, metallic salts including alkali metal, alkaline earth metal and transition metal salts such as, for example, calcium, magnesium, potassium, sodium and zinc salts. Pharmaceutically acceptable base addition salts also include organic salts made from basic amines such as, for example, N,N'-dibenzylethylene-diamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these salts may be prepared from the corresponding compound by reacting, for example, the appropriate acid or base with the compound. As used herein, the term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" means a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, stabilizer, dispersing agent, suspending agent, diluent, excipient, thickening agent, solvent or encapsulating material, involved in carrying or transporting a compound described herein within or to the patient such that it may perform its intended function. Typically, such constructs are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation, including the compound(s) described herein, and not injurious to the patient. Someexamples of materials that may serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; surface active agents; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. As used herein, "pharmaceutically acceptable carrier" also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the compound(s) described herein, and are physiologically acceptable to the patient. Supplementary active compounds may also be incorporated into the compositions. The "pharmaceutically acceptable carrier" may further include a pharmaceutically acceptable salt of the compound(s) described herein. Other additional ingredients that may be included in the pharmaceutical compositions used with the methods or compounds described herein are known in the art and described, for example in Remington's Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985, Easton, PA), which is incorporated herein by reference. The terms "patient," "subject," or "individual" are used interchangeably herein, and refer to any animal, or cells thereof whether in vitro or in situ, amenable to the methods described herein. In a non- limiting embodiment, the patient, subject or individual is a human. As used herein, the term "potency" refers to the dose needed to produce half the maximal response (ED50). A "therapeutic" treatment is a treatment administered to a subject who exhibits signs of pathology, for the purpose of diminishing or eliminating those signs. As used herein, the term "treatment" or "treating" is defined as the application or administration of a therapeutic agent, i.e., a compound or compounds as described herein (alone or in combination with another pharmaceutical agent), to a patient, or application or administration of a therapeutic agent to an isolated tissue or cell line from a patient (e.g., for diagnosis or ex vivo applications), who has a condition contemplated herein or a symptom of a condition contemplated herein, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect a condition contemplated herein, or the symptoms of a condition contemplated herein. Such treatmentsmay be specifically tailored or modified, based on knowledge obtained from the field of pharmacogenomics. If in the present disclosure a structural element is defined that is intended to be part of a formulae disclosed herein and the definition of that structural element does not comprise sufficient free valences to allow the bonding of the remainder of the structural elements of the formula, it is to be assumed that for the purposes of this invention a corresponding structural element is meant in which one or more hydrogen atoms, as needed to fulfil the requirements of the formula, are substituted by a bond to the remainder of the structural elements in this formula. If for example the structural element A in the formula A-B is defined to be a 1H-1,2,3-Triazole, then for the purposes of the present invention it is to be assumed that A is a 1H-1,2,3-Triazo-yl rest, i.e. that one of the hydrogen atoms is substituted by the bond to B. This rule applies unless specified otherwise for certain embodiments. In the formulae of the present disclosure *, or a wavy line, respectively mark the bond that binds the shown partial structure to the remainder of the molecule. In the present disclosure amino acid sequences are stated in the one-letter notation of the IUPAC-IUB as published in the article “IUPAC-IUB Commission of Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences,” Journal of Biological Chemistry, 243 (13): 3557–3559.10 July 1968. doi:10.1016 / S0021-9258(19)34176-6 (https: / / www.jbc.org / article / S0021-9258(19)34176-6 / pdf). In this disclosure amino acids marked with # are part of a disulfide bridge and amino acids marked with * have a N-acetylgalactosamine as O-glycan. Amino acids written in one letter code in small letters are D-amino acids. In the present disclosure compounds are in some cases addressed by a designation “BHXXXX”, wherein BH indicates that the addressed molecule is a target compound of the present invention and “XXXX” are four digits that identify the specific compound (e.g. BH5272). Designations like BH-XXXX, BH000XXXX and BH-000XXXX address the same matter as the designation BHXXXX with the same four digit number. Compositions The compositions containing the compound(s) described herein include a pharmaceutical composition comprising at least one compound as described herein and at least one pharmaceutically acceptable carrier. In certain embodiments, the composition is formulated for an administration route such as oral or parenteral, for example, transdermal, transmucosal (e.g.,sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal and (trans)rectal, intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. Methods of Treatment The compounds of the present invention bind to galactose deficient IgA1 antibodies or to autoantibodies thereof. In various embodiments, and without being bound by theory, by bringing the AG moiety of the compounds of the present invention into proximity of these antibodies through binding of the AG moiety to the hepatocyte asialoglycoprotein receptor, endocytosis and / or degradation of these harmful antibodies can be achieved. The disclosure includes a method of preventing, treating, and / or ameliorating IgA nephropathy in a subject, the method comprising administering to the subject a compound of the present invention or administering to the subject a composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of the present invention. The method includes administering a composition comprising a therapeutically effective amount of a compound of the present invention, and at least one pharmaceutically acceptable carrier. In preferred embodiments, the IgA Nephropathy is aggressive IgA Nephropathy. In other preferred embodiments, the IgA Nephropathy is familial IgA Nephropathy. In various embodiments, the compound of the present invention or the composition is administered by a route selected from the group consisting of oral and parenteral, e.g. transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal, and (trans)rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. In a preferred embodiment the compound of the present invention or the composition is administered intravenously. In various embodiments, the subject is a mammal. In a preferred embodiments, the subject is human. The methods described herein include administering to the subject a therapeutically effective amount of at least one compound described herein, which is optionally formulated in a pharmaceutical composition. In various embodiments, a therapeutically effective amount of at least one compounddescribed herein present in a pharmaceutical composition is the only therapeutically active compound in a pharmaceutical composition. In certain embodiments, the method further comprises administering to the subject an additional therapeutic agent that treats IgA nephropathy or its symptoms. In certain embodiments, administering the compound(s) described herein to the subject allows for administering a lower dose of the additional therapeutic agent as compared to the dose of the additional therapeutic agent alone that is required to achieve similar results in treating IgA nephropathy in the subject. For example, in certain embodiments, the compound(s) described herein enhance(s) the activity of the additional therapeutic compound, thereby allowing for a lower dose of the additional therapeutic compound to provide the same effect. In certain embodiments, the compound(s) described herein and the therapeutic agent are co- administered to the subject. In other embodiments, the compound(s) described herein and the therapeutic agent are co-formulated and co-administered to the subject. In certain embodiments, the subject is a mammal. In preferred embodiments, the mammal is a human. Combination Therapies The compounds useful within the methods described herein can be used in combination with one or more additional therapeutic agents useful for treating IgA nephropathy. These additional therapeutic agents may comprise compounds that are commercially available or synthetically accessible to those skilled in the art. These additional therapeutic agents are known to treat or reduce the symptoms of IgA nephropathy. In various embodiments, compounds of the present invention can be administered either sequentially or concurrently with b1-AR blockers, such as acebutolol, atenolol, betaxolol, bisoprolol, metoprolol, nadolol, propranolol, sotalol, and / or caredilol, and the like. In some embodiments, when b1-AR blockers are co-administered with compounds of the present invention, they can be administered at a lowered dose than if the b1-AR blocker was administered as a monotherapy. In various embodiments, the b1-AR blocker is administered at 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, or 5% of the minimum approved therapeutic dose for the particular b1-AR blocker used in therapy in combination with a compound of the present invention. In various embodiments, co-administration of b1-AR blockers and the compound of the present invention results in fewer, less severe, or no side effects associated with the use of b1-AR blockers.In various embodiments, a synergistic effect is observed when a compound as described herein is administered with one or more additional therapeutic agents or compounds. A synergistic effect may be calculated, for example, using suitable methods such as, for example, the Sigmoid-Emax equation (Holford & Scheiner, 1981, Clin. Pharmacokinet.6:429-453), the equation of Loewe additivity (Loewe & Muischnek, 1926, Arch. Exp. Pathol Pharmacol.114:313-326) and the median-effect equation (Chou & Talalay, 1984, Adv. Enzyme Regul.22:27-55). Each equation referred to above may be applied to experimental data to generate a corresponding graph to aid in assessing the effects of the drug combination. The corresponding graphs associated with the equations referred to above are the concentration-effect curve, isobologram curve and combination index curve, respectively. Administration / Dosage / Formulations The regimen of administration may affect what constitutes an effective amount. The therapeutic formulations may be administered to the subject either prior to or after the onset of IgA nephropathy. Further, several divided dosages, as well as staggered dosages may be administered daily or sequentially, or the dose may be continuously infused, or may be a bolus injection. Further, the dosages of the therapeutic formulations may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation. Administration of the compositions described herein to a patient, preferably a mammal, more preferably a human, may be carried out using known procedures, at dosages and for periods of time effective to IgA nephropathy in the patient. An effective amount of the therapeutic compound necessary to achieve a therapeutic effect may vary according to factors such as the state of the disease or disorder in the patient; the age, sex, and weight of the patient; and the ability of the therapeutic compound to treat IgA nephropathy in the patient. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. A non- limiting example of an effective dose range for a therapeutic compound described herein is from about 1 and 5,000 mg / kg of body weight / per day. One of ordinary skill in the art would be able to study the relevant factors and make the determination regarding the effective amount of the therapeutic compound without undue experimentation. Actual dosage levels of the active ingredients in the pharmaceutical compositions described herein may be varied so as to obtain an amount of the active ingredient that is effective to achieve thedesired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. In particular, the selected dosage level depends upon a variety of factors including the activity of the particular compound employed, the time of administration, the rate of excretion of the compound, the duration of the treatment, other drugs, compounds or materials used in combination with the compound, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well, known in the medical arts. A medical doctor, e.g., physician or veterinarian, having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds described herein employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In particular embodiments, it is especially advantageous to formulate the compound in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the patients to be treated; each unit containing a predetermined quantity of therapeutic compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the compound(s) described herein are dictated by and directly dependent on (a) the unique characteristics of the therapeutic compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding / formulating such a therapeutic compound. In certain embodiments, the compositions described herein are formulated using one or more pharmaceutically acceptable excipients or carriers. In certain embodiments, the pharmaceutical compositions described herein comprise a therapeutically effective amount of a compound described herein and a pharmaceutically acceptable carrier. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity may be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms may be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it is preferable to include isotonic agents, for example, sugars, sodium chloride, or polyalcohols such as mannitol and sorbitol, in the composition. Prolongedabsorption of the injectable compositions may be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate or gelatin. In certain embodiments, the compounds and / or compositions described herein are administered to the patient in dosages that range from one to five times per day or more. In other embodiments, the compounds and / or compositions described herein are administered to the patient in range of dosages that include, but are not limited to, once every day, every two, days, every three days to once a week, and once every two weeks. It is readily apparent to one skilled in the art that the frequency of administration of the compounds and / or various combination compositions described herein varies from individual to individual depending on many factors including, but not limited to, age, disease or disorder to be treated, gender, overall health, and other factors. Thus, administration of the compounds and compositions described herein should not be construed to be limited to any particular dosage regime and the precise dosage and composition to be administered to any patient is determined by the attending physician taking all other factors about the patient into account. The compound(s) described herein for administration may be in the range of from about 1 µg to about 10,000 mg, about 20 µg to about 9,500 mg, about 40 µg to about 9,000 mg, about 75 µg to about 8,500 mg, about 150 µg to about 7,500 mg, about 200 µg to about 7,000 mg, about 350 µg to about 6,000 mg, about 500 µg to about 5,000 mg, about 750 µg to about 4,000 mg, about 1 mg to about 3,000 mg, about 10 mg to about 2,500 mg, about 20 mg to about 2,000 mg, about 25 mg to about 1,500 mg, about 30 mg to about 1,000 mg, about 40 mg to about 900 mg, about 50 mg to about 800 mg, about 60 mg to about 750 mg, about 70 mg to about 600 mg, about 80 mg to about 500 mg, and any and all whole or partial increments therebetween. In various embodiments, compounds of the present invention are administered at a dose of 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mg / kg. In some embodiments, the dose of a compound described herein is from about 1 mg and about 2,500 mg. In some embodiments, a dose of a compound described herein used in compositions described herein is less than about 10,000 mg, or less than about 8,000 mg, or less than about 6,000 mg, or less than about 5,000 mg, or less than about 3,000 mg, or less than about 2,000 mg, or less than about 1,000 mg, or less than about 500 mg, or less than about 200 mg, or less than about 50 mg. Similarly, in some embodiments, a dose of a second compound as described herein is less than about 1,000 mg, or less than about 800 mg, or less than about 600 mg, or less than about 500 mg, or less than about 400 mg, or less than about 300 mg, or less than about 200 mg, or less than about 100 mg, or less than about 50 mg, or less than about 40 mg, or less than about 30 mg, or less than about 25 mg, or less than about 20 mg,or less than about 15 mg, or less than about 10 mg, or less than about 5 mg, or less than about 2 mg, or less than about 1 mg, or less than about 0.5 mg, and any and all whole or partial increments thereof. In a preferred embodiment the compound of the present invention is administered in a dose of 0.01 mg / kg to 20 mg / kg. In a preferred embodiment the composition of the present invention is administered in a dose of 0.01 mg / kg to 20 mg / kg. In certain embodiments, a composition as described herein is a packaged pharmaceutical composition comprising a container holding a therapeutically effective amount of a compound described herein, alone or in combination with a second pharmaceutical agent; and instructions for using the compound to treat, prevent, or reduce one or more symptoms of IgA nephropathy in a patient. Formulations may be employed in admixtures with conventional excipients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for oral, parenteral, nasal, intravenous, subcutaneous, enteral, or any other suitable mode of administration, known to the art. The pharmaceutical preparations may be sterilized and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure buffers, coloring, flavoring and / or aromatic substances and the like. They may also be combined where desired with other active agents, e.g., other analgesic agents. Suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration and the like. It should be understood that the formulations and compositions described herein are not limited to the particular formulations and compositions that are described herein. Oral Administration For oral application, particularly suitable are tablets, dragees, liquids, drops, suppositories, or capsules, caplets and gelcaps. The compositions intended for oral use may be prepared according to any method known in the art and such compositions may contain one or more agents selected from the group consisting of inert, non-toxic pharmaceutically excipients that are suitable for the manufacture of tablets. Such excipients include, for example an inert diluent such as lactose; granulating anddisintegrating agents such as cornstarch; binding agents such as starch; and lubricating agents such as magnesium stearate. The tablets may be uncoated or they may be coated by known techniques for elegance or to delay the release of the active ingredients. Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert diluent. For oral administration, the compound(s) described herein can be in the form of tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., polyvinylpyrrolidone, hydroxypropylcellulose or hydroxypropyl methylcellulose); fillers (e.g., cornstarch, lactose, microcrystalline cellulose or calcium phosphate); lubricants (e.g., magnesium stearate, talc, or silica); disintegrates (e.g., sodium starch glycollate); or wetting agents (e.g., sodium lauryl sulphate). If desired, the tablets may be coated using suitable methods and coating materials such as OPADRY™ film coating systems available from Colorcon, West Point, Pa. (e.g., OPADRY™ OY Type, OYC Type, Organic Enteric OY-P Type, Aqueous Enteric OY-A Type, OY-PM Type and OPADRY™ White, 32K18400). Liquid preparation for oral administration may be in the form of solutions, syrups or suspensions. The liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agent (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (e.g., methyl or propyl p-hydroxy benzoates or sorbic acid). Compositions as described herein can be prepared, packaged, or sold in a formulation suitable for oral or buccal administration. A tablet that includes a compound as described herein can, for example, be made by compressing or molding the active ingredient, optionally with one or more additional ingredients. Compressed tablets may be prepared by compressing, in a suitable device, the active ingredient in a free-flowing form such as a powder or granular preparation, optionally mixed with one or more of a binder, a lubricant, an excipient, a surface active agent, and a dispersing agent. Molded tablets may be made by molding, in a suitable device, a mixture of the active ingredient, a pharmaceutically acceptable carrier, and at least sufficient liquid to moisten the mixture. Pharmaceutically acceptable excipients used in the manufacture of tablets include, but are not limited to, inert diluents, granulating and disintegrating agents, dispersing agents, surface-active agents, disintegrating agents, binding agents, and lubricating agents. Suitable dispersing agents include, but are not limited to, potato starch, sodium starch glycollate, poloxamer 407, or poloxamer 188. One or more dispersing agents can each be individually present in the composition in an amount of about 0.01% w / w to about 90% w / w relative to weight of the dosage form. One or more dispersing agents can each be individually present in the composition inan amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w / w relative to weight of the dosage form. Surface-active agents (surfactants) include cationic, anionic, or non-ionic surfactants, or combinations thereof. Suitable surfactants include, but are not limited to, behentrimonium chloride, benzalkonium chloride, benzethonium chloride, benzododecinium bromide, carbethopendecinium bromide, cetalkonium chloride, cetrimonium bromide, cetrimonium chloride, cetylpyridine chloride, didecyldimethylammonium chloride, dimethyldioctadecylammonium bromide, dimethyldioctadecylammonium chloride, domiphen bromide, lauryl methyl gluceth-10 hydroxypropyl dimonium chloride, tetramethylammonium hydroxide, thonzonium bromide, stearalkonium chloride, octenidine dihydrochloride, olaflur, N-oleyl-1,3-propanediamine, 2-acrylamido-2-methylpropane sulfonic acid, alkylbenzene sulfonates, ammonium lauryl sulfate, ammonium perfluorononanoate, docusate, disodium cocoamphodiacetate, magnesium laureth sulfate, perfluorobutanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluorooctanoic acid, potassium lauryl sulfate, sodium alkyl sulfate, sodium dodecyl sulfate, sodium laurate, sodium laureth sulfate, sodium lauroyl sarcosinate, sodium myreth sulfate, sodium nonanoyloxybenzenesulfonate, sodium pareth sulfate, sodium stearate, sodium sulfosuccinate esters, cetomacrogol 1000, cetostearyl alcohol, cetyl alcohol, cocamide diethanolamine, cocamide monoethanolamine, decyl glucoside, decyl polyglucose, glycerol monostearate, octylphenoxypolyethoxyethanol CA-630, isoceteth-20, lauryl glucoside, octylphenoxypolyethoxyethanol P-40, Nonoxynol-9, Nonoxynols, nonyl phenoxypolyethoxylethanol (NP- 40), octaethylene glycol monododecyl ether, N-octyl beta-D-thioglucopyranoside, octyl glucoside, oleyl alcohol, PEG-10 sunflower glycerides, pentaethylene glycol monododecyl ether, polidocanol, poloxamer, poloxamer 407, polyethoxylated tallow amine, polyglycerol polyricinoleate, polysorbate, polysorbate 20, polysorbate 80, sorbitan, sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, stearyl alcohol, surfactin, Triton X-100, and Tween 80. One or more surfactants can each be individually present in the composition in an amount of about 0.01% w / w to about 90% w / w relative to weight of the dosage form. One or more surfactants can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w / w relative to weight of the dosage form. Suitable diluents include, but are not limited to, calcium carbonate, magnesium carbonate, magnesium oxide, sodium carbonate, lactose, microcrystalline cellulose, calcium phosphate, calciumhydrogen phosphate, and sodium phosphate, Cellactose ® 80 (75 % a-lactose monohydrate and 25 % cellulose powder), mannitol, pre-gelatinized starch, starch, sucrose, sodium chloride, talc, anhydrous lactose, and granulated lactose. One or more diluents can each be individually present in the composition in an amount of about 0.01% w / w to about 90% w / w relative to weight of the dosage form. One or more diluents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w / w relative to weight of the dosage form. Suitable granulating and disintegrating agents include, but are not limited to, sucrose, copovidone, corn starch, microcrystalline cellulose, methyl cellulose, sodium starch glycollate, pregelatinized starch, povidone, sodium carboxy methyl cellulose, sodium alginate, citric acid, croscarmellose sodium, cellulose, carboxymethylcellulose calcium, colloidal silicone dioxide, crosspovidone and alginic acid. One or more granulating or disintegrating agents can each be individually present in the composition in an amount of about 0.01% w / w to about 90% w / w relative to weight of the dosage form. One or more granulating or disintegrating agents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w / w relative to weight of the dosage form. Suitable binding agents include, but are not limited to, gelatin, acacia, pre-gelatinized maize starch, polyvinylpyrrolidone, anhydrous lactose, lactose monohydrate, hydroxypropyl methylcellulose, methylcellulose, povidone, polyacrylamides, sucrose, dextrose, maltose, gelatin, polyethylene glycol. One or more binding agents can each be individually present in the composition in an amount of about 0.01% w / w to about 90% w / w relative to weight of the dosage form. One or more binding agents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w / w relative to weight of the dosage form. Suitable lubricating agents include, but are not limited to, magnesium stearate, calcium stearate, hydrogenated castor oil, glyceryl monostearate, glyceryl behenate, mineral oil, polyethylene glycol, poloxamer 407, poloxamer 188, sodium laureth sulfate, sodium benzoate, stearic acid, sodium stearyl fumarate, silica, and talc. One or more lubricating agents can each be individually present in the composition in an amount of about 0.01% w / w to about 90% w / w relative to weight of the dosage form. One or more lubricating agents can each be individually present in the composition in an amount of atleast, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w / w relative to weight of the dosage form. Tablets can be non-coated or they may be coated using known methods to achieve delayed disintegration in the gastrointestinal tract of a subject, thereby providing sustained release and absorption of the active ingredient. By way of example, a material such as glyceryl monostearate or glyceryl distearate may be used to coat tablets. Further by way of example, tablets may be coated using methods described in U.S. Patent Nos.4,256,108; 4,160,452; and 4,265,874 to form osmotically controlled release tablets. Tablets may further comprise a sweetening agent, a flavoring agent, a coloring agent, a preservative, or some combination of these in order to provide for pharmaceutically elegant and palatable preparation. Tablets can also be enterically coated such that the coating begins to dissolve at a certain pH, such as at about pH 5.0 to about pH 7.5, thereby releasing a compound as described herein. The coating can contain, for example, EUDRAGIT® L, S, FS, and / or E polymers with acidic or alkaline groups to allow release of a compound as described herein in a particular location, including in any desired section(s) of the intestine. The coating can also contain, for example, EUDRAGIT® RL and / or RS polymers with cationic or neutral groups to allow for time controlled release of a compound as described herein by pH- independent swelling. Parenteral Administration For parenteral administration, the compounds as described herein may be formulated for injection or infusion, for example, intravenous, intramuscular or subcutaneous injection or infusion, or for administration in a bolus dose and / or continuous infusion. Suspensions, solutions or emulsions in an oily or aqueous vehicle, optionally containing other formulatory agents such as suspending, stabilizing and / or dispersing agents may be used. Sterile injectable forms of the compositions described herein may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example as a solution in 1, 3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceridederivatives are useful in the preparation of injectables, as are natural pharmaceutically acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as such as lauryl, stearyl, or oleyl alcohols, or similar alcohol. Additional Administration Forms Additional dosage forms suitable for use with the compound(s) and compositions described herein include dosage forms as described in U.S. Patents Nos.6,340,475; 6,488,962; 6,451,808; 5,972,389; 5,582,837; and 5,007,790. Additional dosage forms suitable for use with the compound(s) and compositions described herein also include dosage forms as described in U.S. Patent Applications Nos. 20030147952; 20030104062; 20030104053; 20030044466; 20030039688; and 20020051820. Additional dosage forms suitable for use with the compound(s) and compositions described herein also include dosage forms as described in PCT Applications Nos. WO 03 / 35041; WO 03 / 35040; WO 03 / 35029; WO 03 / 35177; WO 03 / 35039; WO 02 / 96404; WO 02 / 32416; WO 01 / 97783; WO 01 / 56544; WO 01 / 32217; WO 98 / 55107; WO 98 / 11879; WO 97 / 47285; WO 93 / 18755; and WO 90 / 11757. Controlled Release Formulations and Drug Delivery Systems In certain embodiments, the formulations described herein can be, but are not limited to, short- term, rapid-offset, as well as controlled, for example, sustained release, delayed release and pulsatile release formulations. The term sustained release is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that may, although not necessarily, result in substantially constant blood levels of a drug over an extended time period. The period of time may be as long as a month or more and should be a release which is longer that the same amount of agent administered in bolus form. For sustained release, the compounds may be formulated with a suitable polymer or hydrophobic material which provides sustained release properties to the compounds. As such, the compounds for use with the method(s) described herein may be administered in the form of microparticles, for example, by injection or in the form of wafers or discs by implantation. In some cases, the dosage forms to be used can be provided as slow or controlled-release of one or more active ingredients therein using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes,or microspheres or a combination thereof to provide the desired release profile in varying proportions. Suitable controlled-release formulations known to those of ordinary skill in the art, including those described herein, can be readily selected for use with the pharmaceutical compositions described herein. Thus, single unit dosage forms suitable for oral administration, such as tablets, capsules, gelcaps, and caplets that are adapted for controlled-release are encompassed by the compositions and dosage forms described herein. Most controlled-release pharmaceutical products have a common goal of improving drug therapy over that achieved by their non-controlled counterparts. Ideally, the use of an optimally designed controlled-release preparation in medical treatment is characterized by a minimum of drug substance being employed to cure or control the condition in a minimum amount of time. Advantages of controlled-release formulations include extended activity of the drug, reduced dosage frequency, and increased patient compliance. In addition, controlled-release formulations can be used to affect the time of onset of action or other characteristics, such as blood level of the drug, and thus can affect the occurrence of side effects. Most controlled-release formulations are designed to initially release an amount of drug that promptly produces the desired therapeutic effect, and gradually and continually release of other amounts of drug to maintain this level of therapeutic effect over an extended period of time. In order to maintain this constant level of drug in the body, the drug must be released from the dosage form at a rate that will replace the amount of drug being metabolized and excreted from the body. Controlled-release of an active ingredient can be stimulated by various inducers, for example pH, temperature, enzymes, water, or other physiological conditions or compounds. The term "controlled- release component" is defined herein as a compound or compounds, including, but not limited to, polymers, polymer matrices, gels, permeable membranes, liposomes, or microspheres or a combination thereof that facilitates the controlled-release of the active ingredient. In one embodiment, the compound(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation. In one embodiment, the compound(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation. The term delayed release is used herein in its conventional sense to refer to a drug formulation that provides for an initial release of the drug after some delay following drug administration and that mat, although not necessarily, includes a delay of from about 10 minutes up to about 12 hours. The term pulsatile release is used herein in its conventional sense to refer to a drug formulation thatprovides release of the drug in such a way as to produce pulsed plasma profiles of the drug after drug administration. The term immediate release is used in its conventional sense to refer to a drug formulation that provides for release of the drug immediately after drug administration. As used herein, short-term refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes and any or all whole or partial increments thereof after drug administration after drug administration. As used herein, rapid-offset refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes, and any and all whole or partial increments thereof after drug administration. Dosing The therapeutically effective amount or dose of a compound described herein depends on the age, sex and weight of the patient, the current medical condition of the patient and the progression of IgA nephropathy in the patient being treated. The skilled artisan is able to determine appropriate dosages depending on these and other factors. A suitable dose of a compound described herein can be in the range of from about 0.01 mg to about 5,000 mg per day, such as from about 0.1 mg to about 1,000 mg, for example, from about 1 mg to about 500 mg, such as about 5 mg to about 250 mg per day. The dose may be administered in a single dosage or in multiple dosages, for example from 1 to 4 or more times per day. When multiple dosages are used, the amount of each dosage may be the same or different. For example, a dose of 1 mg per day may be administered as two 0.5 mg doses, with about a 12-hour interval between doses. It is understood that the amount of compound dosed per day may be administered, in non- limiting examples, every day, every other day, every 2 days, every 3 days, every 4 days, or every 5 days. For example, with every other day administration, a 5 mg per day dose may be initiated on Monday with a first subsequent 5 mg per day dose administered on Wednesday, a second subsequent 5 mg per day dose administered on Friday, and so on. In the case wherein the patient's status does improve, upon the doctor's discretion the administration of the compound(s) described herein is optionally given continuously; alternatively, thedose of drug being administered is temporarily reduced or temporarily suspended for a certain length of time (i.e., a "drug holiday"). The length of the drug holiday optionally varies between 2 days and 1 year, including by way of example only, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, 35 days, 50 days, 70 days, 100 days, 120 days, 150 days, 180 days, 200 days, 250 days, 280 days, 300 days, 320 days, 350 days, or 365 days. The dose reduction during a drug holiday includes from 10%-100%, including, by way of example only, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%. Once improvement of the patient's conditions has occurred, a maintenance dose is administered if necessary. Subsequently, the dosage or the frequency of administration, or both, is reduced to a level at which the improved disease is retained. In certain embodiments, patients require intermittent treatment on a long-term basis upon any recurrence of symptoms and / or infection. The compounds described herein can be formulated in unit dosage form. The term "unit dosage form" refers to physically discrete units suitable as unitary dosage for patients undergoing treatment, with each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, optionally in association with a suitable pharmaceutical carrier. The unit dosage form may be for a single daily dose or one of multiple daily doses (e.g., about 1 to 4 or more times per day). When multiple daily doses are used, the unit dosage form may be the same or different for each dose. Toxicity and therapeutic efficacy of such therapeutic regimens are optionally determined in cell cultures or experimental animals, including, but not limited to, the determination of the LD50(the dose lethal to 50% of the population) and the ED50(the dose therapeutically effective in 50% of the population). The dose ratio between the toxic and therapeutic effects is the therapeutic index, which is expressed as the ratio between LD50and ED50. The data obtained from cell culture assays and animal studies are optionally used in formulating a range of dosage for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with minimal toxicity. The dosage optionally varies within this range depending upon the dosage form employed and the route of administration utilized.Brief description of the figures The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments of the present application. Figure 1: Figure 1 shows the structure of BH3656, a compound of the present invention. Figure 2: Figure 2 shows the structure of BH3598, a compound of the present invention. Figure 3: Figure 3 shows the structure of BH3706, a compound of the present invention. Figure 4: Figure 4 shows the structure of BH3380, a compound of the present invention. Figure 5: Figure 5 shows the structure of BH3409, a compound of the present invention. Figure 6: Figure 6 shows the structure of BH3707, a compound of the present invention. Figure 7: Figure 7 shows the structure of BH3708, a compound of the present invention. Figure 8: Figure 8 shows the structure of BH3709, a compound of the present invention. Figure 9: Figure 9 shows the structure of BH3734, a compound of the present invention. Figure 10: Figure 10 shows the structure of BH3735, a compound of the present invention. Figure 11: Figure 11 shows the structure of BH3736, a compound of the present invention. Figure 12: Figure 12 shows the structure of BH3737, a compound of the present invention. Figure 13: Figure 13 shows the structure of BH3776, a compound of the present invention. Figure 14: Figure 14 shows the structure of BH3738, a compound of the present invention. Figure 15: Figure 15 shows the structure of BH3739, a compound of the present invention. Figure 16: Figure 16 shows the structure of BH3740, a compound of the present invention. Figure 17: Figure 17 shows the structure of BH3741, a compound of the present invention. Figure 18: Figure 9 shows the structure of BH3777, a compound of the present invention. Figure 19: Figure 19 shows the structure of BH3742, a compound of the present invention. Figure 20: Figure 20 shows the structure of BH3743, a compound of the present invention. Figure 21: Figure 21 shows the structure of BH3744, a compound of the present invention.Figure 22: Figure 22 shows the structure of BH3745, a compound of the present invention. Figure 23: Figure 23 shows the structure of BH3778, a compound of the present invention. Figure 24: Figure 24 shows the structure of BH3592, a compound of the present invention. Figure 25: Figure 25 shows the structure of BH3658, a compound of the present invention. Figure 26: Figure 26 shows the structure of BH3596, a compound of the present invention. Figure 27: Figure 27 shows the structure of BH3597, a compound of the present invention. Figure 28: Figure 28 shows the structure of BH3026, a compound of the present invention. Figure 29: Figure 29 shows the structure of BH3657, a compound of the present invention. Figure 30: Figure 30 shows the structure of BH3555, a compound of the present invention. Figure 31: Figure 31 shows the structure of BH3547, a compound of the present invention. Figure 32: Figure 32 shows the structure of BH3618, a compound of the present invention. Figure 33: Figure 33 shows the structure of BH3595, a compound of the present invention. Figure 34: Figure 34 shows the structure of BH3704, a compound of the present invention. Figure 35: Figure 35 shows the structure of BH3705, a compound of the present invention. Figure 36: Figure 36 shows the structure of BH3619, a compound of the present invention. Figure 37: Figure 37 shows the structure of BH3379, a compound of the present invention. Figure 38: Figure 39 shows the structure of BH3408, a compound of the present invention. Figure 39: Figure 39 shows the structure of BH3078, a compound of the present invention. Figure 40: Figure 40 shows the structure of BH3028, a compound of the present invention. Figure 41: Figure 41 shows the structure of BH3177, a compound of the present invention. Figure 42: Figure 42 shows the structure of BH3079, a compound of the present invention. Figure 43: Figure 43-1 and Figure 43-2 show the procedure for the preparation of intermediate Compound 1431.Figure 44: Figure 44-1 and Figure 44-2 show the procedure for the preparation of BH3487, a compound of the present invention. Figure 44-3 and Figure 44-4 show the structure of BH3487, a compound of the present invention. Figure 45: Figure 45-1 and Figure 45-2 show the procedure for the preparation of intermediate Compound 1432. Figure 46: Figure 46-1, Figure 46-2 and Figure 46-3 show the procedure for the preparation of BH3407, a compound of the present invention. Figure 46-4 and Figure 46-5 show the structure of BH3407. Figure 47: Figure 47-1 and Figure 47-2 show the procedure for the preparation of BH3922, a compound of the present invention. Figures 47-3, 47-6 and 47-7 show the structure of BH3922. Figures 47-4 and 47-5 show the structure of Intermediate 208. Figure 48: Figure 48-1 and Figure 48-2 show the procedure for the preparation of BH3877, a compound of the present invention. Figure 47-3 shows the structure of BH3877. Figure 49: Figure 49-1 and Figure 49-2 show the procedure for the preparation of BH3923, a compound of the present invention. Figure 47-3 shows the structure of BH3923. Figure 50: Figure 50-1 shows the procedure for the preparation of BH3903, a compound of the present invention. Figure 50-2 shows the structure of BH3903. Figure 51: Figure 51 shows the procedure for the preparation of intermediate compound BH3874 and the structure thereof. Figure 52: Figure 52 shows the procedure for the preparation of intermediate compound BH3875 and the structure thereof. Figure 53: Figure 53-1 shows the procedure for the preparation of BH3876, a compound of the present invention. Figure 53-2 shows the structure of BH3876. Figure 54: Figure 54 shows the procedure for the preparation of intermediate compound BH3878 and the structure thereof. Figure 55: Figure 55 shows the procedure for the preparation of intermediate compound BH3879 and the structure thereof.Figure 56: Figure 56-1 shows the procedure for the preparation of BH3880. Figure 56-2 shows the structure of BH3880. Figure 57: Figure 57 shows the structure of intermediate compound BH3879. Figure 58: Figure 58 shows the development over time of the blood level of galactose deficient IgA antibodies in vivo in mice after an IV dosage of BH3596. It also shows the comparison blood level of galactose deficient IgA antibodies without BH3596 only. Figure 59: Figure 59 shows the development over time of the blood level of galactose deficient IgA antibodies in vivo in mice after an IV dosage of BH3597. It also shows the comparison blood level of galactose deficient IgA antibodies without BH3597 only.ŅxamplesExamples Various embodiments of the present application can be better understood by reference to the following examples which are offered by way of illustration. The scope of the present application is not limited to the examples given herein. Synthetic examples General Chemistry Methods Flash chromatography was performed on a CombiFlash NEXTGEN 300+ system by Teledyne ISCO running software version 5.0.62. Separation was accomplished on RediSep Rf High performance gold C18 columns (reverse phase) and RediSep Rf flash columns (normal phase). HPLC purification of compounds was performed using a Shimadzu chromatography system using a Waters SunFire C18 OBD Prep Column (10 mm x 150 mm) and the LabSolutions Software Version 5.92. NMR analysis was performed on Agilent DD2400 MHz and Agilent DD2600 MHz NMR spectrometers. The 600 MHz instrument was equipped with a C[H] cold probe. HRMS analysis was performed on a Shimadzu 9030 Quadrupole Time-of- Flight LC-MS system following separation on a Shim-pack Scepter C18-1201.9 µm (2.1 x 50 mm) reverse phase chromatography column. Separation was performed using a gradient of water to acetonitrile with the addition of 0.1% formic acid. Infrared (IR) spectra were collected using neat samples and recorded using a Thermo Nicolet 6700 equipped with a diamond ATR cell. Select νma are reported in cm-1. Optical rotation was recorded on a Rudolph Autopol IV polarimeter. Chemicals were purchased from Sigma Aldrich, Fisher, and Carbosynth. Solvents were purchased from Fisher and Macron. Further methods and procedures If not otherwise mentioned, further methods and procedures have been performed as disclosed in WO 2023 / 028590 A1, especially from page 47 to page 52. EXAMPLE 1. Procedure for preparation of alkyne Intermediate 4.

[0001] Preparation of Intermediate 2.To a solution of commercially available material 1 (30.0 g, 135.59 mmol, 1.00 equiv.) in DMF (80 mL) was added commercially available material 1A (96.78 g, 813.56 mmol, 70.13 mL, 6.00 equiv.), followed by the addition of finely powdered KOH (45.65 g, 813.56 mmol, 6.00 equiv.) in small portions. The reaction mixture was stirred at 25oC for 24 h. TLC (Petroleum ether: Ethyl acetate = 5:1, Rf = 0.64) indicated 1 was consumed completely and many new spots formed. The reaction mixture was diluted with water and extracted with EtOAc (50 mL * 3). The combined organic layers were washed with brine (50 mL * 2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate = 1 / 0 to 1 / 1) to give Intermediate 2 (17.6 g, 52.48 mmol, 38.7% yield) as yellow oil.

[0002] Preparation of Intermediate 3.To a solution of Intermediate 2 (16.0 g, 47.71 mmol, 1.00 equiv.) in dichloromethane (DCM, 160 mL) was added trifluoroacetic acid (TFA, 98.56 g, 864.39 mmol, 64.00 mL, 18.12 equiv.) and the mixture was stirred at 25 °C for 1 h. LCMS showed Intermediate 2 was consumed completely and one main peak with desired mass was detected. The reaction mixture was concentrated under reduced pressure to afford Intermediate 3 (20.0 g, crude, TFA salt) as yellow oil.

[0003] Preparation of Intermediate 4.To a solution of commercially available material 3A (1.56 g, 7.44 mmol, 1.00 equiv.) in DMF (10 mL) was added O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium- hexafluorphosphat (HATU, 2.83 g, 7.44 mmol, 1.00 equiv.) and DIEA (4.81 g, 37.19 mmol, 6.48 mL, 5.00 equiv.) at 0oC, the mixture was stirred at 0oC for 0.5 h, Intermediate 3 (1.75 g, 7.44 mmol, 1.00 equiv.) was added to the mixture. The mixture was stirred at 20oC for 2 h. LCMS showed 3A was consumed, several new peaks were shown on LCMS and the desired MS was detected. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (20 mL * 3). The combined organic layer was washed with brine (20 mL * 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate = 10 / 1 to 5 / 1) to afford Intermediate 4 (1.02 g, 2.39 mmol, 32.1% yield) as a white solid. LCMS: RT = 2.188 min, MS cal.: 426.2, found: [M + H]+= 427.3.1NMR (400 MHz, CDCl3) δ = 7.40 - 7.29 (m, 5H), 6.08 (s, 1H), 5.40 (br s, 1H), 5.13 (s, 2H), 4.13 (d, J = 1.7 Hz, 6H), 3.84 (s, 6H), 2.44 (t, J = 2.3 Hz, 3H). EXAMPLE 2. Procedure for preparation of BH-0003672 / Target A011A. Example 2a. Intermediate 6

[0004] Preparation of Intermediate 6.To a solution of commercially available Intermediate 5 (1S,2R,3R,4R,5S)-4-amino-1- (hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3-diol, 5.00 g, 26.15 mmol, 1.00 equiv.) inpyridine (Py, 100 mL) was added propanoyl propanoate (27.23 g, 209.23 mmol, 8.00 equiv.). The mixture was stirred at 20oC for 12 h. LCMS showed the desired mass was detected and the reactant was consumed. The reaction mixture was concentrated under reduced pressure to afford Intermediate 6 (10.86 g, crude) as yellow oil, it was used in the next step without further purification. LCMS: RT = 0.715 min, MS cal.: 415.2, found: [M + H]+= 416.2. Example 2b. Intermediate 7

[0005] Preparation of Intermediate 7.To a solution of Intermediate 6 (5.40 g, 13.00 mmol, 1.00 equiv.) in MeOH (50 mL) was added NaOMe (2.81 g, 51.99 mmol, 4.00 equiv.). The mixture was stirred at 20oC for 2 h. LCMS showed the desired mass and the reactant was consumed. The reaction mixture was neutralized by addition of 1M HCl. The resulting solution was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, DCM / MeOH=10 / 1 to 5 / 1) to give Intermediate 7 (4.20 g, 16.99 mmol, 65.3% yield) as a yellow solid. LCMS: RT = 0.174 min, MS cal.: 247.1, found: [M + H]+= 248.3.1H NMR (400 MHz, CD3OD) δ = 5.23 (d, J = 1.4 Hz, 1H), 4.01 - 3.69 (m, 5H), 2.42 - 2.20 (m, 2H), 1.27 - 1.04 (m, 3H). Example 2c. Intermediate 8

[0006] Preparation of Intermediate 8:To a solution of Intermediate 7 (2.10 g, 8.49 mmol, 1.00 equiv.) in DMF (15 mL) was added [(1S,4R)-7,7- dimethyl-2-oxo-norbornan-1-yl]methanesulfonic acid (1.06 g, 4.25 mmol, 0.50 equiv.) and Intermediate 7A (4.42 g, 42.47 mmol, 5.00 equiv.). The mixture was stirred at 70oC for 12 h. LCMS showed the desired mass and the reactant was consumed. The reaction mixture was diluted with water (30 mL) and extracted with EtOAc (30 mL * 3). The combined organic layer was washed with brine (30 mL * 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate = 3 / 1 to 0 / 1) to give Intermediate 8 (4.25 g, 14.79 mmol, 87.0% yield) as a white solid. LCMS: RT = 0.426 min, MS cal.: 287.1, found: [M + H]+= 288.2.1H NMR (400 MHz, CD3OD) δ = 5.23 (s, 1H), 4.59 (s, 1H), 4.30 (d, J = 5.7 Hz, 1H), 4.18 (t, J = 6.4 Hz, 1H), 3.97 - 3.68 (m, 6H), 2.30 - 2.17 (m, 2H), 1.49 (s, 3H), 1.34 (s, 3H), 1.14 (t, J = 7.6 Hz, 3H). Example 2d. Intermediate 9

[0007] Preparation of Intermediate 9:To a solution of commercially available material 8 (2.20 g, 7.66 mmol, 1.00 equiv.) in THF (20 mL) was added NaH (3.06 g, 76.57 mmol, 60%, 10.00 equiv.) at 0oC. The mixture was stirred at 0oC for 0.5 h, then was added Intermediate 8A (4.54 g, 13.78 mmol, 1.80 equiv.) at 0oC, the mixture was stirred at 20oC for 1 h. LCMS showed the desired mass and the reactant was consumed. The reaction mixture was diluted with water (20 mL) and extracted with DCM (20 mL * 3). The combined organic layers were washed with brine (20 mL * 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate = 2 / 1 to 0 / 1) to give Intermediate 9 (3.70 g, 7.57 mmol, 49.4% yield) as a white solid. LCMS: RT = 1.475 min, MS cal.: 488.2, found: [M + H]+= 489.3.1H NMR (400 MHz, CDCl3) δ = 5.60 (br d, J = 8.8 Hz, 1H), 5.33 (d, J = 2.0 Hz, 1H), 4.21 (d, J = 5.9 Hz, 1H), 4.27 - 4.19 (m, 1H), 4.19 - 4.10 (m, 1H), 4.04 - 3.92 (m, 2H), 3.86 - 3.74 (m, 3H), 3.76 - 3.58 (m, 15H), 3.43 - 3.34 (m, 2H), 2.31 - 2.21(m, 2H), 1.55 (s, 3H), 1.38 - 1.32 (m, 3H), 1.20 - 1.12 (m, 3H).Example 2e. Intermediate 10

[0008] Preparation of Intermediate 10:To a solution of Intermediate 4 (552 mg, 1.28 mmol, 99.0% purity, 1.00 equiv.), Intermediate 9 (1.88 g, 3.84 mmol, 3.00 equiv.) in DMSO (8 mL) was added sodium ascorbate (634.65 mg, 3.20 mmol, 2.50 equiv.) and CuSO4.5H2O (319.95 mg, 1.28 mmol, 1.00 equiv.). The mixture was stirred at 25oC for 2 h. LCMS showed the desired mass and the reactant was consumed. The reaction mixture was diluted with water (20 mL) and extracted with dichloromethane (DCM, 10 mL *3). The combined organic layers were washed with brine (10 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by pre-HPLC (column: Waters Xbridge Prep OBD C18150*40mm*10μm; mobile phase: [water (NH4HCO3)-ACN]; B%: 30%-60%, 8 min) to give Intermediate 10 (1.25 g, 660.66 μmol, 51.5% yield) as yellow oil. LCMS: RT = 2.065 min, MS cal.: 1891.9, mass observed: [M + 2H]2+= 947.2.1H NMR (400MHz, DMSO-d6) δ ppm 8.06 - 7.99 (m, 6H), 7.40 - 7.27 (m, 6H), 5.15 (d, J = 1.9 Hz, 3H), 5.03 (s, 2H), 4.55 - 4.43 (m, 12H), 4.24 (d, J =5.9 Hz, 3H), 4.17 - 4.11 (m, 3H), 3.84 - 3.78 (m, 12H), 3.76 - 3.69 (m,6H), 3.67 - 3.62 (m, 9H), 3.62 - 3.55 (m, 7H), 3.54 - 3.43 (m, 32H), 2.13 (q, J = 7.6 Hz, 6H), 1.39 (s, 9H), 1.30 - 1.22 (m, 9H), 0.99 (t, J = 7.6 Hz, 9H). Example 2f. Intermediate 11

[0009] Preparation of Intermediate 11:To a solution of Intermediate 10 (400 mg, 211.41 μmol, 1.00 equiv.) in THF (1 mL) was added Pd / C (200 mg, 10%). The mixture was stirred at 20oC for 2 h under H2(15 Psi). LCMS showed the desired mass and the reactant was consumed. The reaction mixture was filtered and concentrated under reduced pressure to give Intermediate 11 (330.3 mg, 187.89 μmol, 88.9% yield) as yellow oil. LCMS: RT = 1.810 min, MS cal.: 1757.9, mass observed: [M + 2H]2+= 880.1.1H NMR (400 MHz, DMSO-d6) δ = 8.05 - 7.99 (m, 6H), 5.16 (d, J = 2.0 Hz, 3H), 4.55 - 4.45 (m, 13H), 4.25 (d, J = 5.9 Hz, 3H), 4.15 - 4.10 (m, 3H), 3.84 - 3.56 (m, 35H), 3.53 - 3.46 (m, 32H), 2.13 (q, J = 7.5 Hz, 6H), 1.40 (s, 9H), 1.27 (s, 9H), 0.99 (t, J = 7.6 Hz, 9H). Example 2g. Target A011A (BH-0003672)

[0010] Preparation of BH-0003672 / Target A011A:A mixture of Intermediate 11 (90.0 mg, 51.20 μmol, 1.00 equiv.) in HCl / H2O (2.0 M, 1.0 mL) and MeCN (0.5 mL) was stirred at 20 °C for 1 h. The mixture was lyophilized to afford Target A011A (85.0 mg, 45.69 μmol, 90% purity, 89.2% yield, HCl salt) as a colorless solid. LCMS: RT = 0.705 min, MS cal.: 1637.73, found: [M + 2H]2+= 819.600. EXAMPLE 3. Procedure for preparation of Target A088.

[0011] Preparation of Target A088:

[0012] Preparation of Intermediate 13, 14 and 15 was performed by following the procedure mentioned in Example 1. In the preparation of Intermediate 13, Intermediate 1A, sodium iodide and Tetra-n-butylammonium iodide where used.

[0013] Intermediate 13 (5 g, 18.70 mmol, 23.8% yield) as yellow oil. LCMS: RT = 2.025 min, MS cal.: 267.15, [M – Boc + H]+= 168.21H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.90 (br s, 1 H), 4.17 (d, J = 2.38 Hz, 4 H), 3.87 - 3.99 (m, 1 H), 3.87 - 3.99 (m, 1 H), 3.62 - 3.66 (m, 2 H), 3.56 - 3.61 (m, 2 H)2.44 (t, J = 2.38 Hz, 2 H), 1.45 (s, 9 H).

[0014] Intermediate 14 (3.7 g, 18.17 mmol, 97.1% yield, HCl) as a white solid. LCMS: RT = 1.017 min, MS cal.: 167.09, [M + H]+= 168.2.1H NMR (400 MHz, METHANOL-d4) δ ppm 4.26 (d, J = 2.38 Hz, 4 H), 3.76 - 3.82 (m, 2 H), 3.68 - 3.74 (m, 2 H), 3.56 - 3.63 (m, 1 H), 2.96 (t, J = 2.38 Hz, 2 H).

[0015] Intermediate 15 (5 g, 13.95 mmol, 94.7% yield) as a white solid. LCMS: RT = 1.829 min, MS cal.: 358.15, [M + H]+= 359.3.1H NMR (400 MHz, DMSO-d6) δ ppm 7.86 (d, J = 8.25 Hz, 1 H), 7.26 - 7.45 (m, 6 H), 5.03 (s, 2 H), 4.14 (d, J = 2.25 Hz, 4 H), 4.02 - 4.07 (m, 1 H), 3.61 (d, J = 6.13 Hz, 2 H), 3.39 - 3.49 (m, 6 H).

[0016] Preparation of Intermediate 16 was performed by following the procedure of Example 2e mutatis mutandis. Intermediate 16 (0.30 g, 224.64 μmol, 24.7% yield) as yellow oil. LCMS: RT = 1.868 min, MS cal.: 1334.6, [M + 2H]2+= 668.8.1H NMR (400 MHz, DMSO-d6) δ ppm 8.08 - 7.98 (m, 4H), 7.80 (d, J = 8.3 Hz, 1H), 7.39 - 7.30 (m, 5H), 5.15 (d, J = 1.9 Hz, 2H), 5.02 (s, 2H), 4.56 - 4.45 (m, 8H), 4.23 (d, J = 5.9 Hz, 2H), 4.12 (t, J = 6.6 Hz, 2H), 4.03 (td, J = 5.7, 7.9 Hz, 1H), 3.84 - 3.77 (m, 8H), 3.75 - 3.67 (m, 4H), 3.67 - 3.54 (m, 8H), 3.54 - 3.40 (m, 25H), 2.12 (q, J = 7.5 Hz, 4H), 1.39 (s, 6H), 1.26 (s, 6H), 0.98 (t, J = 7.6 Hz, 6H).

[0017] Preparation of Intermediate 17 was performed by following the procedure mentioned in Example 2f mutatis mutandis. Intermediate 17 (250.0 mg, 208.10 μmol, 79.4% yield) as colorless oil. LCMS: RT = 1.559 min, MS cal.: 1200.6, [M + 2H]2+= 601.7.1H NMR (400 MHz, DMSO-d6) δ = 8.05 - 7.99 (m, 3H), 5.15 (d, J = 1.6 Hz, 1H), 4.50 (s, 5H), 4.24 (d, J = 5.9 Hz, 2H), 4.12 (t, J = 6.6 Hz, 2H), 4.08 - 3.98 (m, 1H), 3.82 - 3.77 (m, 7H), 3.74 - 3.54 (m, 15H), 3.41 (br s, 25H), 2.12 (q, J = 7.6 Hz, 4H), 1.89 (s, 1H), 1.76 (td, J = 3.2, 6.5 Hz, 4H), 1.39 (s, 6H), 1.26 (s, 6H), 0.98 (t, J = 7.6 Hz, 6H).

[0018] Preparation of Target A088 was performed by following the procedure mentioned in Example 2g for Target A011A mutatis mutandis. Target A088 (88.0 mg, 76.13 μmol, 91.5% yield, 97.0% purity) as yellow oil. LCMS: RT = 1.174 min, MS cal.: 1120.5, [M + 2H]2+= 561.6.1H NMR (400 MHz, DMSO- d6) δ = 8.41 (d, J = 8.3 Hz, 1H), 8.06 (s, 2H), 8.02 (br s, 2H), 7.80 (d, J = 7.6 Hz, 2H), 5.08 (d, J = 1.0 Hz, 2H), 4.54 - 4.48 (m, 8H), 4.09 (br dd, J = 5.6, 7.9 Hz, 2H), 3.85 - 3.40 (m, 51H), 2.12 (q, J = 7.6 Hz, 4H), 0.98 (t, J = 7.6 Hz, 6H).EXAMPLE 4. Procedure for Preparation of Target A089.

[0019] Preparation of Intermediate 18:To a solution of 17A (100 mg, 492.14 μmol, 1.00 equiv.) in dichloromethane (DCM, 1 mL) was added oxalyl dichloride (74.96 mg, 590.56 μmol, 51.70 μL, 1.2 equiv.) and dimethylformamide (DMF, 3.60 mg, 49.21 μmol, 3.79 μL, 0.1 equiv.) at 0 °C. The mixture was stirred at 0°C for 0.5 hr. Then Intermediate 17 (140 mg, 116.54 μmol, 1.0 equiv.) and diisopropylethylamine (DIEA, 129.10 mg, 998.90 μmol, 173.99 μL, 3.0 equiv.) was added to the mixture. The mixture was stirred at 25 °C for 0.5 h. LCMS showed Intermediate 17 was consumed completely and one main peak with desired mass was detected. After filtration, Intermediate 18 was obtained as colorless liquid used for the next step directly. LCMS: RT = 1.738 min, MS cal.: 1385.7, [M + 2H]2+= 694.3.

[0020] Preparation of Target A089To a solution of HCl (3 M, 4.00 mL, 36.17 equiv.) was added Intermediate 18. The mixture was stirred at 40 °C for 1 h. LCMS showed Intermediate 18 was consumed completely and one main peak with desired mass was detected. The reaction mixture was filtered. The filtrate was purified by prep-HPLC (column: Phenomenex C1880 * 40 mm * 3 μm; mobile phase: [water (NH4HCO3)-acetonitrile (CAN)]; B%: 15%-35%, 8 min) to afford Target A089 (100.6 mg, 77.05 μmol, 23.2% yield, 100% purity) as colorless oil. LCMS: RT = 1.357 min, MS cal.: 1305.6, [M + 2H]2+= 654.3.1H NMR (400 MHz, METHANOL-d4) δ = 8.04 (s, 2H), 5.20 (s, 2H), 4.61 - 4.57 (m, 7H), 4.21 (br t, J = 5.4 Hz, 1H), 3.99 - 3.86 (m, 12H), 3.78 - 3.70 (m, 7H), 3.67 - 3.56 (m, 37H), 3.38 - 3.34 (m, 3H), 2.53 (t, J = 6.1 Hz, 2H), 2.26 (q, J = 7.5 Hz, 4H), 1.13 (t, J = 7.6 Hz, 6H). EXAMPLE 5. Procedure for Preparation of BH-0003552 / Target A090.

[0021] Preparation of Intermediate 20, 21 and Target A090 were performed by following the procedure disclosed in Example 2 for Intermediates 10 and 11 and for Target A011A mutatis mutandis.

[0022] Intermediate 20 (300 mg, 385.19 μmol, 49.8% yield) as yellow oil. LCMS: RT = 1.793 min, MS cal.: 778.4, [M + H]+= 779.6.1NMR (400 MHz, CDCl3) δ = 7.74 (s, 1H), 7.41 - 7.29 (m, 5H), 6.58 (br s, 1H), 5.76 (br d, J = 8.1 Hz, 1H), 5.63 (br s, 1H), 5.33 (d, J = 1.9 Hz, 1H), 5.13 (s, 2H), 4.64 (s, 2H), 4.53 (t, J = 4.9 Hz, 2H), 4.19 (d, J = 5.9 Hz, 1H), 4.13 (ddd, J = 2.0, 6.8, 8.8 Hz, 1H), 4.05 - 3.98 (m, 1H), 3.94 (d, J = 10.1 Hz, 1H), 3.90 - 3.84 (m, 4H), 3.83 - 3.72 (m, 2H), 3.66 (br s, 3H), 3.65 - 3.55 (m, 12H), 2.25 (dq, J = 2.8, 7.6 Hz, 2H), 1.63 (s, 2H), 1.56 (s, 3H), 1.35 (s, 3H), 1.16 (t, J = 7.6 Hz, 3H).

[0023] Intermediate 21 (200 mg, 310.22 μmol, 60.4% yield) as yellow oil. LCMS: RT = 1.124 min, MS cal.: 644.3, [M + H]+= 645.4.1H NMR (400 MHz, CDCl3) δ = 7.92 (br s, 1H), 7.80 (s, 1H), 6.02 (br d, J = 8.6 Hz, 1H), 5.33 (d, J = 1.5 Hz, 1H), 4.69 - 4.59 (m, 3H), 4.55 (br t, J = 4.9 Hz, 2H), 4.17 (br d, J = 5.8 Hz, 2H), 4.14 - 4.01 (m, 3H), 3.96 - 3.54 (m, 30H), 3.50 - 3.39 (m, 3H), 2.25 (dq, J = 2.3, 7.6 Hz, 2H), 1.55 (s, 3H), 1.34 (s, 3H), 1.14 (t, J = 7.5 Hz, 3H).

[0024] BH-0003552 / Target A090 (60 mg, 99.23 μmol, 91.4% yield) as colorless oil. LCMS: RT = 1.471 min, MS cal.: 604.3, [M + H]+= 605.2.1H NMR (400 MHz, MeOH-d4) δ = 8.51(s, 1H), 5.20(s, 1H), 4.82- 4.75 (m, 4H), 4.00 - 3.95 (m, 2H), 3.94 - 3.86 (m, 3H), 3.79 - 3.74 (m, 3H), 3.73 - 3.69 (m, 3H), 3.68 - 3.57 (m, 14H), 3.52 - 3.47 (m, 2H), 2.29 (q, J = 7.6 Hz, 2H), 1.14 (t, J = 7.6 Hz, 3H). EXAMPLE 6. Procedure for Preparation of Target A091.

[0025] Preparation of Intermediate 23.To a solution of commercially available material 22 (150 mg, 738.21 μmol, 1.00 equiv.) in DCM (2 mL) was added oxalyl chloride (112.44 mg, 885.85 μmol, 77.54 μL, 1.20 equiv.) at 0 °C and the reaction was stirred for 1 h at 0 °C. TLC (petroleum ether: ethyl acetate = 1: 1, the starting material Rf = 0.2 product Rf = 0.5) showed the reaction was completed. Intermediate 23 (160 mg, 721.89 μmol, crude) was used to next step directly.

[0026] Preparation of Intermediate 25.To solution of Intermediate 24 (396.6 mg, 615.25 μmol, 1.00 equiv.) and DIEA (238.55 mg, 1.85 mmol, 321.49 μL, 3.00 equiv.) in DCM (1 mL) was added Intermediate 24 (150 mg, 676.77 μmol, 1.10 equiv.) at 0 °C and the reaction was stirred for 1 h at 25 °C. LCMS showed the reaction was completed. The reaction was concentrated under reduced pressure to give Intermediate 25 (300.0 mg, 361.49 μmol, 58.8% yield) as yellow oil.

[0027] Preparation of Intermediate Target A091.A mixture of Intermediate 25 (300.0 mg, 361.49 μmol, 1.00 equiv.) in HCl (3 M, 5 mL) was degassed and purged with N2for 3 times, and then the mixture was stirred at 40oC for 1 h under N2atmosphere. LCMS showed the reaction was completed. The reaction was concentrated under reduced pressure to give crude product. The crude product was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18150 * 40 mm * 10 μm; mobile phase: [water (NH4HCO3)-ACN]; B%: 5%-35%, 8min) to give Target A091 (106.0 mg, 134.21 μmol, 37.1% yield) as white oil. LCMS: RT = 1.219 min, MS cal.: 789.4, [MNMR (400 MHz, MeOH-d4) δ = 8.04 (s, 1H), 5.20 (d, J = 1.3 Hz, 1H), 4.63 - 4.56 (m, 4H), 3.98 - 3.85 (m, 8H), 3.79 - 3.75 (m, 3H), 3.73 (br d, J = 4.3 Hz, 1H), 3.71 (br d, J = 4.4 Hz, 1H), 3.68 - 3.65 (m, 4H), 3.65 - 3.63 (m, 5H), 3.63 - 3.59 (m, 9H), 3.58 - 3.54 (m, 2H), 3.39 (td, J = 5.1, 17.4 Hz, 4H), 2.53 (t, J = 6.1 Hz, 2H), 2.26 (q, J = 7.6 Hz, 2H), 1.13 (t, J = 7.6 Hz, 3H). EXAMPLE 7. Procedure for Preparation of BH-0003368 / Target A068.

[0028] Preparation of Intermediate 26.To a solution of Intermediate 22 (12.71 mg, 62.57 μmol, 1.10 equiv.) in DMF (1 mL) was added HATU (23.79 mg, 62.57 μmol, 1.10 equiv.) and DIEA (22.06 mg, 170.66 μmol, 3.00 equiv.) at 0 °C. After the mixture was stirred at 0 °C for 0.5 h, Intermediate 11 (100 mg, 56.89 μmol, 1.00 equiv.) was added at 0 °C, then the mixture was stirred at 20 °C for 1 h. LCMS showed the reactant was consumed and desired mass was detected. The reaction mixture residue was diluted with water (10 mL) and extracted with DCM (10 mL * 3). The combined organic layers were washed with brine (10 mL*3), dried over Na2SO4, filtered and concentrated under reduced pressure to give Intermediate 26 (90.0 mg, 46.32 μmol, 81.4% yield) as yellow oil which was used for next step directly. LCMS: RT = 1.954 min, MS cal.: 1943.1, found: [M + 2H]2+= 972.7.

[0029] Preparation of Target A068.The solution of Intermediate 26 (90.0 mg, 46.32 μmol, 1.00 equiv.) in HCl (1 M, 2.25 mL, 48.58 equiv.) was stirred at 20 °C for 1 h. LCMS showed the reactant was consumed and desired mass was detected. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was purified by prep-HPLC (column: C18-1150 * 30 mm * 5 μm; mobile phase: [water (NH4HCO3)-ACN]; B%: 20%-50%, 10min) to give Target A068 (28.1 mg, 15.41 μmol, 33.3% yield) as yellow oil. LCMS: RT = 1.490 min, MS cal.: 1822.9, found: [M + 2H]2+= 912.7.1H NMR (400 MHz, DMSO-d6) δ = 8.01 (s, 4H), 7.78 (d, J = 7.9 Hz, 3H), 7.26 (s, 1H), 5.07 (d, J = 1.0 Hz, 3H), 4.82 (d, J = 5.5 Hz, 3H), 4.56 - 4.44 (m, 15H), 3.85 - 3.77 (m, 9H), 3.76 - 3.69 (m, 3H), 3.69 - 3.61 (m, 13H), 3.61 - 3.56 (m, 9H), 3.55 - 3.43 (m, 42H), 3.39 - 3.34 (m, 5H), 2.37 (br t, J = 6.7 Hz, 2H), 2.12 (q, J = 7.5 Hz, 6H), 0.98 (t, J = 7.6 Hz, 9H). EXAMPLE 8. Procedure for Preparation of BH-0003024 / Target A001A.

[0030] Preparation of Intermediate 28.To a solution of commercially available material 27 (20.0 g, 134.06 mmol, 1.00 equiv.) in MeOH (40 mL) was added TEA (31.2 g, 308.34 mmol, 43 mL, 2.30 equiv.) and benzylchloroformate (CbzCl, 25.2 g, 147.47 mmol, 21 mL, 1.10 equiv.) in MeOH (20 mL) dropwise at 20 °C and the reaction was stirred for 12 h at 20 °C. LCMS showed the reaction was completed. The reaction was poured into H2O (100 mL) and extracted with DCM (50 mL x 2). The combined organic layer was washed with brine (100 mL), dried over anhydrousNa2SO4, filtered and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, dichloromethane: methanol = 100: 1 to 10: 1) to give Intermediate 28 (65 g, 229.42 mmol, 85.0% yield) as colorless oil. LCMS: RT = 0.700 min, MS cal.: 283.1, found: [M + H]+= 284.2.1H NMR (400 MHz, CDCl3) δ = 7.41 - 7.29 (m, 5H), 5.47 - 5.34 (m, 1H), 5.16 - 5.06 (m, 2H), 3.78 - 3.69 (m, 2H), 3.64 (s, 4H), 3.41 (br d, J = 3.9 Hz, 2H), 2.50 - 2.35 (m, 1H).

[0031] Preparation of Intermediate 30.To a solution of commercially available material 29 (5.00 g, 12.84 mmol, 1.00 equiv.) in DCM (500 mL) was added FeCl3(6.25 g, 38.53 mmol, 3.00 equiv.) at 25oC and the reaction was stirred for 3 h at 25oC. TLC (DCM: MeOH = 10: 1, the starting material Rf= 0.5, product Rf= 0.4) showed the reaction was completed. The reaction solution was poured into H2O (50 mL) and extracted with DCM (20 mL x 2). The combined organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give Intermediate 30 (3.6 g, 10.93 mmol, 85.1% yield) as yellow oil which was used to the next step without further purification.1H NMR (400 MHz, CDCl3) δ = 6.01 (d, J = 6.8 Hz, 1H), 5.49 - 5.44 (m, 1H), 4.92 (dd, J = 3.2, 7.4 Hz, 1H), 4.30 - 3.96 (m, 5H), 2.13 (s, 3H), 2.10 - 2.00 (m, 10H), 1.57 (br s, 2H).

[0032] Preparation of Intermediate 31.To a solution of Intermediate 30 (9.00 g, 27.33 mmol, 1.00 equiv.) and 28 (6.97 g, 24.60 mmol, 0.90 equiv.) in DCM (90 mL) was added trimethylsilyltrifluormethansulfonat (TMSOTf, 1.82 g, 8.20 mmol, 0.30 equiv.) at 0 °C. Then the reaction was stirred at 25 °C for 12 h. LCMS showed the desired product was obtained. The reaction was filtered and the filtrate was poured into H2O (100 mL) and DCM (100 mL x 2). Thecombined organic layer was washed with brine (200 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude, then purified by reversed-phase HPLC (0.1% NH3.H2O) to give Intermediate 31 (28 g, 45.71 mmol, 55.7% yield) as yellow oil. LCMS: RT = 1.540 min, MS cal.: 612.3, found: [M + H]+= 613.4.1H NMR (400 MHz, CDCl3) δ = 7.41 - 7.30 (m, 5H), 6.26 (br d, J = 9.1 Hz, 1H), 5.49 (br s, 1H), 5.31 (s, 1H), 5.25 (br s, 1H), 5.12 (s, 2H), 5.08 - 5.00 (m, 1H), 4.74 (br d, J = 8.5 Hz, 1H), 4.26 - 4.00 (m, 3H), 3.96 - 3.77 (m, 3H), 3.75 - 3.53 (m, 8H), 3.49 - 3.31 (m, 2H), 2.17 - 2.12 (m, 3H), 2.04 (s, 3H), 2.01 - 1.89 (m, 6H).

[0033] Preparation of Intermediate 32.To a solution of Intermediate 31 (22.00 g, 35.91 mmol, 1.00 equiv.) in THF (6.2 mL) was added Pd / C (8 g, 35.91 mmol, 10%) and TFA (6.14 g, 53.87 mmol, 3.99 mL, 1.50 equiv.) at 25 °C and the reaction was stirred for 1 h at 25 °C under H2. LCMS showed the desired product was obtained. The reaction was filtered and the filtrate was concentrated under reduced pressure to give Intermediate 32 (20.00 g, 33.75 mmol, 94.0% yield, TFA) as yellow oil which was used to the next step without further purification. LCMS: RT = 0.645 min, MS cal.: 478.2, found: [M + H]+= 479.2.1H NMR (400 MHz, MeOD) δ = 5.49 (s, 1 H), 5.35 (d, J = 2.76 Hz, 1 H), 5.05 (dd, J = 11.17, 3.39 Hz, 1 H), 4.58 (d, J = 8.41 Hz, 1 H), 3.93 - 4.19 (m, 5 H), 3.63 - 3.76 (m, 9 H), 3.15 (t, J = 4.96 Hz, 2 H), 2.14 (s, 3 H), 2.03 (s, 3 H), 1.95 (d, J = 2.38 Hz, 6 H).

[0034] Preparation of Intermediate 34.To a solution of commercially available material 33 (44.0 g, 363.23 mmol, 52.38 mL, 1.00 equiv.) in DMSO (73 mL) was added NaOH (5 M, 7 mL, 0.01 equiv.) while stirring, followed by the addition of 33A (158.3 g, 1.23 mol, 179.26 mL, 3.40 equiv.) dropwise at 20 °C, then the mixture was stirred at 20 °C for 24 h. LCMS showed the desired mass was detected and Intermediate 33 was consumed. Two parallel reactions were combined. The reaction was filtered and the filtrate was concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, dichloromethane: methanol = 100:1 to 10:1) to give Intermediate 34 (118.00 g, 233.37 mmol, 32.1% yield) as colorless oil. LCMS: RT = 0.781 min, MS cal.: 505.3, found: [M + H]+= 506.3.

[0035] Preparation of Intermediate 35.To a solution of Intermediate 34 (38.0 g, 75.15 mmol, 1.00 equiv.) in CH2Cl2(323 mL) and Na2CO3(31.9 g, 75.15 mmol, 25%, 1.00 equiv.) was added while stirring. Then CbzCl (39.7 g, 232.97 mmol, 3.00 equiv.) was added dropwise and the reaction mixture was stirred for 24 h at 20 °C. TLC (Petrolum ether: ethyl acetate = 5:1, the starting material Rf = 0.5, product Rf = 0.3) showed the reaction was completed. Three parallel reactions were combined for work up. The reaction was filtered and the filtrate was concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, Petroleum ether: ethyl acetate = 100:1 to 10:1) to give Intermediate 35 (104.7 g, 163.67 mmol, 72.6% yield) as colorless oil.

[0036] Preparation of Intermediate 36.Intermediate 35 (25.7 g, 40.17 mmol, 1.00 equiv.) was added HCOOH (400 mL) and then the reaction was stirred at 20 °C for 18 h. After completion, four parallel reactions were combined for work up. The reaction solution was concentrated under reduced pressure to give Intermediate 36 (17.0 g, 89.8% yield) as colorless oil which was used for next step directly without further purification.

[0037] Preparation of Intermediate 37.To a solution of Intermediate 36 (2.0 g, 4.24 mmol, 1.00 equiv.) in DMF (30 mL) was added HATU (5.2 g, 13.58 mmol, 3.20 equiv.), DIEA (3.84 g, 29.70 mmol, 5.17 mL, 7.00 equiv.) at 25 °C was added Intermediate 32 (8.8 g, 14.85 mmol, 3.50 equiv., TFA) at 0 °C and the reaction was stirred at 25 °C for 12 h. LCMS showed one main peak with desired Ms was detected. The reaction was poured into H2O (50 mL) and extracted with DCM (50 mL x 2). The combined organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, dichloromethane: methanol = 100: 1 to 10: 1) to give Intermediate 37 (6.20 g, 3.35 mmol, 78.9% yield) as a yellow solid. LCMS: RT = 0.781 min, MS cal.: 505.3, found: [M + H]+= 506.3.1H NMR (400MHz, CHLOROFORM-d) δ ppm 7.04 - 6.87 (m, 2H), 6.78 - 6.54 (m, 2H), 5.33 (d, J = 3.1 Hz, 2H), 5.17 (dd, J = 3.3, 11.2 Hz, 2H), 5.04 (s, 1H), 4.78 (d, J = 8.5 Hz, 2H), 4.24 - 4.05 (m, 6H), 3.99 - 3.87 (m, 4H), 3.82 - 3.74 (m, 2H), 3.73 - 3.49 (m, 24H), 3.47 - 3.35 (m, 4H), 2.42 (br t, J = 5.8 Hz, 4H), 2.19 - 2.12 (m, 6H), 2.05 (s, 6H), 1.97 (d, J = 14.1 Hz, 11H).

[0038] Preparation of Intermediate 38.To a solution of Intermediate 37 (2.00 g, 1.08 mmol, 1.00 equiv.) in THF (1 mL) was added Pd / C (0.1 g, 1.08 mmol, 10%) and TFA (184.6 mg, 1.62 mmol, 1.5 equiv.) at 25 °C and the reaction was stirred for 0.5 h at 25 °C. LCMS showed the desired product was obtained. The reaction was filtered and the filtrate was concentrated under reduced pressure to give Intermediate 38 (5.5 g, 3.00 mmol, 92.7% yield, TFA) as yellow oil which was used for next step without further purification. LCMS: RT = 0621 min, MS cal.: 1717.8, found: [M + 2H]2+= 860.5.1HNMR (400 MHz, CHLOROFORM-d) δ = 8.33 - 7.80 (m, 3H), 7.10 - 6.88 (m, 3H), 5.34 (br d, J = 3.1 Hz, 3H), 5.21 (br dd, J = 3.1, 11.1 Hz, 3H), 4.99 (br dd, J = 3.1, 10.8 Hz, 1H), 4.88 - 4.80 (m, 3H), 4.73 (br d, J = 8.1 Hz, 1H), 4.21 - 4.01 (m, 10H), 4.00 - 3.89 (m, 7H), 3.77 (br d, J = 5.0 Hz, 11H), 3.68 - 3.53 (m, 34H), 3.47 - 3.35 (m, 6H), 2.47 (br d, J = 5.1 Hz, 6H), 2.16 - 2.12 (m, 9H), 2.05 - 2.03 (m, 9H), 1.97 (d, J = 11.6 Hz, 18H).

[0039] Preparation of Intermediate 39.To a solution of 3A (500.0 mg, 2.39 mmol, 1.00 equiv.) in DMF (1 mL) was added HATU (999.7 mg, 2.63 mmol, 1.10 equiv.) and DIEA (617.8 mg, 4.78 mmol, 832.62 μL, 2.00 equiv.) at 0 °C and the reaction was stirred for 0.5 h at 0oC. Then Intermediate 38 (4.11 g, 2.39 mmol, 1.00 equiv.) was added at 0 °C and the mixture was stirred for 0.5 h at 0 °C. LCMS showed the desired product was obtained. The reaction was poured into H2O (10 mL) and extracted with DCM (5mL x 2). The combined organic layer was washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, dichloromethane: methanol = 100: 1 to 3: 1) to give Intermediate 39 (7.0 g, 3.67 mmol, 76.7% yield) as a white solid. LCMS: RT = 1.702 min, MS cal.: 1908.8, found: [M + 2H]2+= 956.1.1H NMR (400 MHz, CDCl3) δ = 7.38 - 7.30 (m, 5H), 7.02 - 6.65 (m, 7H), 5.34 (d, J = 2.9 Hz, 3H), 5.24 - 5.09 (m, 5H), 4.92 (br dd, J = 2.9, 10.6 Hz, 1H), 4.79 (d, J = 8.5 Hz, 3H), 4.70 (br d, J = 8.1 Hz, 1H), 4.20 - 4.05 (m, 9H), 3.97 - 3.84 (m, 9H), 3.83 - 3.74 (m, 3H), 3.71 - 3.55 (m, 38H), 3.48 - 3.37 (m, 6H), 2.42 (br s, 6H), 2.15 (s, 9H), 2.05 (s, 9H), 1.98 (d, J = 14.4 Hz, 18H).

[0040] Preparation of Intermediate 40.To a solution of Intermediate 39 (5.0 g, 2.62 mmol, 1.00 equiv.) in THF (10 mL) was added Pd / C (0.25 g, 2.62 mmol, 10%) and TFA (447.8 mg, 3.93 mmol, 1.50 equiv.) at 25 °C and the reaction was stirred at 25 °C for 1 h. LCMS showed the reaction was completed. The reaction was filtered and the filtrate was concentrated under reduced pressure to give Intermediate 40 (3.7 g, 2.02 mmol, 77.2% yield, 97.0% purity) as a light-yellow solid. LCMS: RT = 2.405 min, MS cal.: 1774.8, found: [M + 2H]2+= 888.5.1H NMR (400 MHz, DMSO-d6) δ = 8.03 - 7.91 (m, 5H), 7.85 (br d, J = 9.1 Hz, 3H), 7.76 (s, 1H), 5.23 (br d, J = 2.9 Hz, 3H), 4.99 (br dd, J = 3.1, 11.3 Hz, 3H), 4.56 (br d, J = 8.5 Hz, 3H), 4.05 (s, 8H), 3.94 - 3.86 (m, 3H), 3.84 - 3.77 (m, 3H), 3.65 - 3.47 (m, 36H), 3.42 (br t, J = 5.7 Hz, 6H), 3.28 - 3.18 (m, 6H), 2.33 (br t, J = 5.9 Hz, 6H), 2.12 (s, 9H), 2.02 (s, 9H), 1.91 (s, 9H), 1.79 (s, 9H).

[0041] Preparation of Target A001A.To a solution of Intermediate 40 (1.0 g, 563.13 μmol, 1.00 equiv.) in MeOH (10 mL) was added NaOMe (30.4 mg, 563.13 μmol, 1.00 equiv.). The mixture was stirred at 20 °C for 2 h. LCMS showed the reactant was consumed and the desired mass was detected. The reaction mixture was filtered and concentrated under reduced pressure to give Target A001A (600.0 mg, 429.35 μmol, 76.2% yield) as yellow solid. LCMS: RT = 1.455 min, MS cal.: 1397.47, found: [M + 2H]2+= 699.4.1H NMR (400MHz, DMSO-d6) δ = 7.94 (br t, J = 5.7 Hz, 3H), 7.64 - 7.55 (m, 3H), 4.67 - 4.43 (m, 6H), 4.28 (d, J = 8.5 Hz, 3H), 3.83 - 3.61 (m, 9H), 3.59 - 3.13 (m, 86H), 2.38 - 2.23 (m, 6H), 1.80 (s, 8H). EXAMPLE 9. Procedure for Preparation of BH-0003556 / Target A073.

[0042] Preparation of Intermediate 42.To a solution of commercially available 41 (D-(+)-Galactosamine, 40.00 g, 185.50 mmol, 1.00 equiv., HCl) in pyridine (200 mL) was added 41 (193.13 g, 1.48 mol, 191.22 mL, 8.00 equiv.). The mixture was stirred at 20 °C for 12 h. LCMS showed the desired compound was detected and the reactant was consumed. The mixture was diluted with 1M HCl (100 mL) and extracted with EtOAc (100 mL*3), the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. Theresidue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate=100 / 1 to 1 / 1) to give Intermediate 42 (19.70 g, 42.87 mmol, 23.1% yield) as colorless oil. LCMS: RT = 0.815 min, MS cal.: 459.2, [M - 73]+= 386.4.

[0043] Preparation of Intermediate 43.To a solution of Intermediate 42 (5.00 g, 10.88 mmol, 1.00 equiv.) in DCM (50 mL) was added TiCl4(2.72 g, 14.36 mmol, 1.32 equiv.). The mixture was stirred at 20°C for 12 h. TLC (PE: EA=2:1, Rf = 0.5) showed the reactant was consumed and one main spot was formed. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate=1 / 9 to 0 / 1) to give Intermediate 43 (4.5 g, crude) as a yellow solid.

[0044] Preparation of Intermediate 44.A solution of Intermediate 43 (4.00 g, 9.48 mmol, 1.00 equiv.) in toluene (100 mL) was stirred at 20 °C for 0.5 h, then to the mixture was added azobis(isobutyronitril) (AIBN, 467.1 mg, 2.84 mmol, 0.30 equiv.) and Bu3SnH (5.52 g, 18.96 mmol, 5.02 mL, 2.00 equiv.) at 20 °C. The mixture was stirred at 125 °C for 2 h. LCMS showed the desired mass was detected and the reactant was consumed. The reaction mixture was added to saturated solution KF (50 mL) and extracted with EtOAc (50 mL * 3). The combined organic layers were washed with brine (50 mL * 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate=10 / 1 to 1 / 1) to give Intermediate 44 (1.28 g, 3.31 mmol, 35.2% yield) as a white solid. LCMS: RT= 1.804 min, MS cal.: 387.2, [M + H]+= 388.3.1H NMR (400MHz, MeOD-d4) δ = 5.42 (dd, J = 0.9, 3.3 Hz, 1H), 4.99 (dd, J = 3.3, 11.1 Hz, 1H), 4.34 (dt, J = 5.3, 11.1 Hz, 1H), 4.14 - 4.06 (m, 2H), 4.06 - 3.97 (m, 2H), 3.96 - 3.88 (m, 2H), 2.45 (q, J = 7.4 Hz, 2H), 2.35 - 2.29 (m, 2H), 2.28 - 2.20 (m, 2H), 2.19 - 2.11 (m, 2H), 1.16 (t, J = 7.6 Hz, 3H), 1.13 - 1.04 (m, 9H).

[0045] Preparation of Intermediate 45.To a solution of Intermediate 44 (3.5 g, 9.03 mmol, 1.00 equiv.) in MeOH (30 mL) was added NaOMe (488.05 mg, 9.03 mmol, 1.00 equiv.). The mixture was stirred at 25 °C for 12 h. TLC (DCM: MeOH =10:1, Rf = 0.3) showed the reactant was consumed and one new spot was formed. The reaction mixture was filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, DCM / MeOH=20 / 1 to 5 / 1) to give Intermediate 45 (1.6 g, 7.30 mmol, 80.8% yield) as a white solid.1H NMR (400MHz, MeOD-d4) δ = 4.17 (dt, J = 5.1, 10.7 Hz, 1H), 3.96 (dd, J = 5.2, 10.9 Hz, 1H), 3.88 (d, J = 2.9 Hz, 1H), 3.80 - 3.73 (m, 1H), 3.72 - 3.66 (m, 1H), 3.54 (dd, J = 3.2, 10.6 Hz, 1H), 3.46 - 3.39 (m, 1H), 3.10 (t, J = 10.9 Hz, 1H), 2.31 - 2.20 (m, 2H), 1.19 - 1.12 (m, 3H).

[0046] Preparation of Intermediate 46.To a solution of Intermediate 45 (440.0 mg, 2.01 mmol, 1.00 equiv.) in DMF (10 mL) was added [(1S,4R)- 7,7-dimethyl-2-oxo-norbornan-1-yl]methanesulfonic acid (251.19 mg, 1.00 mmol, 0.50 equiv.) and 7A (1.05 g, 10.03 mmol, 1.23 mL, 5.00 equiv.). The mixture was stirred at 70 °C for 12 h. LCMS showed the desired mass was detected and the reactant was consumed. The reaction mixture was diluted withNaHCO3(10 mL) and extracted with EtOAc (10 mL * 3). The combined organic layers were washed with brine (5 mL *3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, DCM: MeOH = 30 / 1 to 10 / 1) to give Intermediate 46 (450.0 mg, 1.74 mmol, 86.5% yield) as a yellow solid. LCMS: RT=0.522 min, MS cal.: 259.1, [M + H]+= 260.3.1H NMR (400MHz, MeOD-d4) δ = 4.24 (d, J = 4.8 Hz, 1H), 4.13 - 3.98 (m, 2H), 3.90 - 3.69 (m, 4H), 3.08 (t, J = 11.0 Hz, 1H), 2.31 - 2.20 (m, 2H), 1.52 (s, 3H), 1.35 (s, 3H), 1.15 (t, J = 7.6 Hz, 3H).

[0047] Preparation of Intermediate 47.To a solution of Intermediate 46 (4.00 g, 15.43 mmol, 1.00 equiv.) in DMF (30 mL) was added NaH (9.25 g, 231.39 mmol, 60%, 15.00 equiv.) at 0 °C. The mixture was stirred at 0 °C for 0.5 h.8A (12.69 g, 38.57 mmol, 2.50 equiv.) was added at 0 °C, and the mixture was stirred at 20 °C for 1 h. LCMS showed the desired mass was detected and the reactant was consumed. The reaction mixture was diluted with ice- water (50 mL) and extracted with DCM (50 mL * 3). The combined organic layers were washed with brine (50 mL * 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, DCM: MeOH = 30 / 1 to 10 / 1) to give Intermediate 47 (4.2 g, 9.12 mmol, 59.1% yield) as yellow oil. LCMS: RT = 1.632 min, MS cal.: 460.2, [M + H]+= 461.2.1H NMR (400MHz, MeOD-d4) δ = 5.38 (br d, J = 7.3 Hz, 1H), 4.09 - 3.92 (m, 3H), 3.90 - 3.84 (m, 1H), 3.79 - 3.66 (m, 15H), 3.43 - 3.34 (m, 2H), 3.22 - 3.13 (m, 1H), 2.27 - 2.16 (m, 2H), 1.54 (s, 3H), 1.34 (s, 3H), 1.14 (t, J = 7.5 Hz, 3H).

[0048] Preparation of Intermediate 48.To a solution of Intermediate 47 (907.1 mg, 1.97 mmol, 3.00 equiv.), Intermediate 4 (280.0 mg, 656.57 μmol, 1.00 equiv.) in DMSO (5 mL) was added CuSO4.5H2O (163.9 mg, 656.57 μmol, 1.00 equiv.) and sodium ascorbate (325.2 mg, 1.64 mmol, 2.50 equiv.). The mixture was stirred at 20 °C for 1 h. LCMS showed the desired mass was detected and the reactant was consumed. The reaction mixture was filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex C1880 * 40 mm * 3 μm; mobile phase: [water (NH4HCO3)-ACN]; B%: 20%-45%, 8min) to give Intermediate 48 (500.0 mg, 276.55 μmol, 42.1% yield) as yellow oil. LCMS: RT = 2.091 min, MS cal.: 1806.9, [M + 2H]2+= 904.7.

[0049] Preparation of Intermediate 49.To a solution of Intermediate 48 (140.0 mg, 77.43 μmol, 1.00 equiv.) in THF (2 mL) was added Pd / C (70.0 mg, 77.43 μmol, 10%). The mixture was stirred at 20 °C for 0.2 h. LCMS showed the desired mass was detected and the reactant was consumed. The reaction mixture was filtered and concentrated to give Intermediate 49 (120.0 mg, 71.69 μmol, 92.6% yield) as yellow oil. LCMS: RT = 1.272 min, MS cal.: 1672.9, [M + 2H]2+= 837.7.1H NMR (400MHz, MeOD-d4) δ = 8.01 (s, 3H), 4.62 - 4.53 (m, 13H), 4.19 (dd, J = 2.1, 5.0 Hz, 3H), 4.08 - 4.03 (m, 3H), 4.01 - 3.94 (m, 3H), 3.90 (t, J = 5.0 Hz, 6H), 3.87 - 3.81 (m, 4H), 3.81 - 3.75 (m, 9H), 3.72 - 3.67 (m, 6H), 3.66 - 3.56 (m, 38H), 3.19 (s, 2H), 3.08 - 2.98 (m, 3H), 2.26 - 2.18 (m, 6H), 1.49 (s, 9H), 1.31 (s, 9H), 1.12 (t, J = 7.6 Hz, 9H).

[0050] Preparation of Target BH-0003556 / A073.The solution of Intermediate 49 (160.0 mg, 95.59 μmol, 1.00 equiv.) in HCl (1 M, 95.59 μL, 1.00 equiv.) was stirred at 20 °C for 1 h. LCMS showed the desired mass was detected and the reactant was consumed. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters Xbridge BEH C18100 * 30 mm * 10 μm; mobile phase: [water (NH4HCO3)- ACN]; B%: 1%-20%, 8min) to give Target A073 (55.0 mg, 35.40 μmol, 37.0% yield) as a white solid. LCMS: RT = 1.043 min, MS cal.: 1552.8, [M + 2H]2+= 777.7.1H NMR (400MHz, MeOD-d4) δ = 8.02 (s, 3H), 4.61 - 4.55 (m, 12H), 4.13 (dt, J = 5.3, 10.8 Hz, 3H), 3.91 (ddd, J = 3.2, 5.0, 7.9 Hz, 9H), 3.85 (d, J = 2.9 Hz, 3H), 3.76 (s, 6H), 3.68 - 3.64 (m, 9H), 3.63 - 3.58 (m, 35H), 3.54 - 3.50 (m, 6H), 3.07 (t, J = 10.9 Hz, 3H), 2.23 (dq, J = 1.6, 7.6 Hz, 6H), 1.12 (t, J = 7.6 Hz, 9H). EXAMPLE 10. Procedure for Preparation of Target A076, A076A, A076B, A076C.

[0051] Preparation of Intermediate 50.To a solution of 5 (4.00 g, 20.92 mmol, 1.00 equiv.) in H2O (40 mL) was added NaHCO3(4.39 g, 52.31 mmol, 2.03 mL, 2.50 equiv.) under N2 at 25 °C, then to the reaction was added benzyl chloroformate (5.71 g, 33.48 mmol, 4.76 mL, 1.60 equiv.) at 0 °C and the reaction was stirred for 12 h at 25 °C. TLC (petroleum ether : ethyl acetate = 0 : 1, product Rf = 0.5) showed the reaction was completed. The reaction was poured into H2O (10 mL) and extracted with EtOAc (30 mL x 2). The combined organic layer was washed with brine (30 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, petroleum ether: ethyl acetate = 100 : 1 to 1 : 1) to give Intermediate 50 (3.9 g, 11.99 mmol, 57.3% yield) as white solid.1H NMR (400 MHz, METHANOL-d4) δ = 7.40 - 7.26 (m, 5H), 5.09 (s, 2H), 3.94 - 3.77 (m, 3H), 3.75 - 3.64 (m, 4H).

[0052] Preparation of Intermediate 51.To a solution of Intermediate 50 (830.0 mg, 2.55 mmol, 1.00 equiv.) in acetone (47 mL) was added H2SO4 (32.5 mg, 331.68 μmol, 17.68 μL, 0.13 equiv.) at 25 °C and the reaction was stirred for 4 h at 50 °C. LCMS showed the reaction was completed. The reaction was concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, dichloromethane: methanol = 10: 1) to give Intermediate 51 (750.0 mg, 2.05 mmol, 80.4% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ = 7.41 - 7.30 (m, 5H), 5.40 (s, 1H), 5.20 - 5.06 (m, 2H), 5.02 (br d, J = 9.1 Hz, 1H), 4.21 - 4.01 (m, 3H), 3.93 - 3.80 (m, 3H), 3.79 - 3.66 (m, 3H), 1.58 (s, 3H), 1.37 (s, 3H).

[0053] Preparation of Intermediate 52.To a solution of Intermediate 51 (300.0 mg, 821.07 μmol, 1.00 equiv.) in THF (5 mL) was added NaH (328.4 mg, 8.21 mmol, 60%, 10.00 equiv.) at 0 °C and the reaction was stirred for 0.5 h at 0 °C. Then the reactionwas added Intermediate 8A (405.4 mg, 1.23 mmol, 1.50 equiv.) at 25 °C and the reaction was stirred for 0.5 h at 25 °C. LCMS showed the reaction was completed. The reaction was poured into H2O (2 mL) and extracted with DCM (3 mL x 2). The combined organic layer was washed with brine (5 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (SiO2, petroleum ether: ethyl acetate = 100: 1 to 10 : 1) to give Intermediate 52 (107.0 mg, 188.85 μmol, 23.0% yield) as yellow oil. LCMS: RT = 2.294 min, MS cal.: 556.2, [M + H2O + H]+= 584.5.1H NMR (400 MHz, DMSO-d6) δ = 7.62 (d, J = 8.1 Hz, 1H), 7.41 - 7.23 (m, 5H), 5.03 (s, 2H), 4.22 (d, J = 5.9 Hz, 1H), 4.18 - 4.11 (m, 1H), 3.84 - 3.54 (m, 10H), 3.48 - 3.42 (m, 1H), 3.39 (t, J = 4.9 Hz, 2H), 1.43 - 1.36 (m, 3H), 1.29 - 1.25 (m, 3H).

[0054] Preparation of Intermediate 53.To a solution of Intermediate 52 (90.0 mg, 229.33 μmol, 1.00 equiv.) and Intermediate 4 (389.8 mg, 687.99 μmol, 3.00 equiv.) in DMSO (4 mL) was added sodium ascorbate (159.0 mg, 802.66 μmol, 3.50equiv.) and CuSO4.5H2O (57.3 mg, 229.33 μmol, 1.00 equiv.) at 20 °C and the reaction was stirred for 1 h at 20 °C. LCMS showed the reaction was completed. The reaction was concentrated under reduced pressure to give crude product. The crude product was purified by prep-HPLC (column: Waters Xbridge BEH C18100 * 30 mm * 10 μm; mobile phase: [water (NH4HCO3)-ACN]; B%: 50%-80%, 8 min) to give Intermediate 53 (170.0 mg, 81.25 μmol, 35.4% yield) as a yellow solid. LCMS: RT = 2.754 min, MS cal.: 2091.0, [M + 2H]2+= 1047.3.1H NMR (400 MHz, CDCl3) δ = 7.72 (s, 2H), 7.39 - 7.30 (m, 13H), 5.36 (s, 3H), 5.28 - 5.20 (m, 2H), 5.19 - 5.01 (m, 6H), 4.57 (s, 5H), 4.53 (br t, J = 5.0 Hz, 5H), 4.20 (d, J = 5.8 Hz, 3H), 4.04 (br t, J = 6.3 Hz, 3H), 3.94 (br d, J = 10.1 Hz, 3H), 3.90 - 3.74 (m, 21H), 3.73 - 3.65 (m, 7H), 3.65 - 3.57 (m, 25H), 3.43 - 3.27 (m, 3H), 1.57 (br s, 9H), 1.42 (s, 9H), 1.36 (s, 9H), 1.03 (br t, J = 6.8 Hz, 4H).

[0055] Preparation of Intermediate 54.To a solution of Intermediate 53 (200.0 mg, 95.59 μmol, 1.00 equiv.) in MeOH (1 mL) was added Pd / C (50.0 mg, 10%) at 25 °C under H2(15 Psi) and the reaction was stirred for 1 h at 25 °C. LCMS showed the reaction was completed. The reaction was filtered and the filtrate was concentrated under reduced pressure to give Intermediate 54 (160.0 mg, 94.68 μmol, 99.0% yield) as a white solid. LCMS: RT = 1.819 min, MS cal.: 1688.9, [M + 2H]2+= 846.1H NMR (400 MHz, CDCl3) δ = 5.31 (s, 1H), 5.26 (d, J = 1.9 Hz, 2H),4.58 (s, 6H), 4.55 (t, J = 5.3 Hz, 6H), 4.16 (d, J = 5.9 Hz, 3H), 3.96 - 3.87 (m, 12H), 3.84 - 3.76 (m, 14H), 3.75 - 3.67 (m, 10H), 3.67 - 3.59 (m, 30H), 2.81 (s, 1H), 2.78 (dd, J = 2.0, 6.5 Hz, 3H), 1.50 (s, 9H), 1.42 (s, 9H), 1.35 (s, 9H).

[0056] Preparation of Target A076To a solution of Intermediate 54 (15.0 mg, 8.88 μmol, 1.00 equiv.) in Py (0.5 mL) was added TFAA (31.7 mg, 150.90 μmol, 20.99 μL, 17.00 equiv.) and 4-dimethylaminopyridine (DMAP, 1.6 mg, 13.31 μmol, 1.50 equiv.) at 0 °C and the reaction mixture was stirred for 3 h at 25 °C. LCMS showed the reaction was completed. The reaction was concentrated under reduced pressure to give crude product. The crude product was purified by prep-HPLC (column: Phenomenex Luna C18100 * 30 mm * 5 μm; mobile phase: [water (TFA)-ACN]; B%: 35%-65%, 10min) to give product. The product was dissolved in DCM (1 mL), then TFA (1.73 mg, 15.17 μmol, 1.12 μL, 10.00 equiv.) was added to the mixture. The mixture was stirred at 25 °C for 12 h. LCMS showed Intermediate 54 was consumed completely and one main peak with desiredmass was detected. It was concentrated under reduced pressure to give Target A076 (2.2 mg, 1.25 μmol, 82.5% yield) as a white solid. LCMS: RT = 1.651 min, MS cal.: 1757.55, mass observed: [M + 2H]2+= 789.9.1H NMR (400 MHz, METHANOL-d4) δ = 8.01 (s, 3H), 5.26 (s, 3H), 4.62 - 4.52 (m, 12H), 4.04 - 3.98 (m, 3H), 3.95 - 3.87 (m, 14H), 3.82 - 3.54 (m, 54H).

[0057] Preparation of Target A076A.To a solution of Intermediate 54 (22.00 mg, 13.02 μmol, 1.00 equiv.) in Py (1 mL) was added DMAP (477.15 ug, 3.91 μmol, 0.30 equiv.) and Ac2O (7.97 mg, 78.11 μmol, 7.32 μL, 6.00 equiv.). The mixture was stirred at 35 °C for 12 h. It was concentrated under reduced pressure to give a residue. The residue was dissolved in DCM (1 mL) and TFA (13.19 mg, 115.64 μmol, 8.56 μL, 10.00 equiv.) was added to the mixture. The mixture was stirred at 25 °C for 12 h. LC-MS showed it was finished and one main peak with desired mass was detected. It was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (neutral condition: column: Phenomenex C18 75*30mm*3μm;mobile phase: [water( NH4HCO3)-ACN];B%: 5%-35%,8min). Target A076A (4.40 mg, 2.68 μmol, 23.2% yield, 97.3% purity)was obtained as a white solid. LCMS: RT = 1.274 min, MS cal.: 1594.7, found: [M + 2H]2+= 798.9.1H NMR (400 MHz, DMSO-d6) δ = 8.01 (s, 3H), 7.89 (d, J = 7.9 Hz, 3H), 7.66 (s, 1H), 5.08 (d, J = 1.0 Hz, 3H), 4.83 (br d, J = 5.1 Hz, 3H), 4.56 (br d, J = 7.0 Hz, 3H), 4.51 (t, J = 5.3 Hz, 7H), 4.48 (s, 6H), 3.82 - 3.78 (m, 9H), 3.76 - 3.70 (m, 4H), 3.68 - 3.58 (m, 17H), 3.53 - 3.46 (m, 40H), 3.02 (s, 2H), 1.83 (s, 9H).

[0058] Preparation of Target A076B.To a solution of Intermediate 54 (30.0 mg, 17.75 μmol, 1.00 equiv.) in Py (1.5 mL) was added DMAP (650.66 μg, 5.33 μmol, 0.30 equiv.) and isobutyricanhydride (14.0 mg, 88.77 μmol, 14.72 μL, 5.00 equiv.). The mixture was stirred at 40 °C for 1 h. Then HCl (3 M, 1mL) was added to the reaction mixture and stirred at 40 °C for 1 h. LCMS showed Intermediate 54 was consumed completely and one main peak with desired mass was detected. It was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters Xbridge BEH C18250 * 50 mm * 10 μm; mobile phase: [water (TFA)-ACN]; B%: 10%-45%, 8min). Target A076B (13.6 mg, 7.17 μmol, 40.4% yield) was obtained as a white solid. LCMS: RT = 2.194 min, MS cal.: 1900.12, mass observed: [M + 2H]2+= 951.2.1H NMR (400MHz, METHANOL-d4) δ = 8.01 (s, 3H), 7.94 (br d, J =8.0 Hz, 1H), 5.21 (d, J =1.3 Hz, 3H), 4.63 - 4.54 (m, 12H), 3.97- 3.86 (m, 14H), 3.78 - 3.70 (m, 15H), 3.69 - 3.63 (m, 16H), 3.62 - 3.57 (m, 25H), 2.60 - 2.46 (m, 3H), 1.12 (d, J =6.9 Hz, 18H).

[0059] Preparation of Target A076C.To a solution of Intermediate 54 (40.0 mg, 23.67 μmol, 1.00 equiv.) in Py (1 mL) was added DMAP (867.54 μg, 7.10 μmol, 0.30 equiv.) and cyclopropanecarbonyl cyclopropanecarboxylate (54A, 10.9 mg, 71.01 μmol, 3.00 equiv.). The mixture was stirred at 40 °C for 12 h. Then HCl (3 M, 1mL) was added to the reaction mixture and stirred at 40 °C for 1 h. LCMS showed Intermediate 54 was consumed completely and one main peak with desired mass was detected. The reaction was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters Xbridge BEH C18100 * 30 mm * 10 μm; mobile phase: [water (TFA)-ACN]; B%: 10%-45%, 8 min). Target A076C (15.0 mg, 7.92 μmol, 33.5% yield) was obtained as a white solid. LCMS: RT = 2.153 min, MS cal.: 1894.07, mass observed:[M + 2H]2+= 948.2.1H NMR (400MHz, METHANOL-d4) δ = 8.03 (s, 3H), 5.23 (s, 3H), 4.63 - 4.57 (m, 12H), 4.01 - 3.87 (m, 15H), 3.81 - 3.76 (m, 11H), 3.73 - 3.65 (m, 15H), 3.64 - 3.60 (m, 27H), 1.73 - 1.64 (m, 3H), 1.32 (br s, 3H), 0.92 - 0.85 (m, 6H), 0.82 - 0.74 (m, 6H). EXAMPLE 11. Procedure for preparation of BH0003599 / Compound 1498, BH0003600 / Compound 1499, BH0003601 / Compound 1500, BH0003620 / Compound 1558 and BH0003621 / Compound 1559.Example 11a. Preparation of BH0003599

[0060] Preparation of Intermediate 55 (sidechain protected resin-bound peptide).

[0061] Peptide was synthesized using standard Fmoc chemistry (Rink AM resin). 1) Loading: To the vessel containing Rink Amide AM resin (3.12 g, 1.00 mmol, 0.32 mmol / g) and DMF (40 mL) was bubbled with N2 for 2 h at 25 °C. Then 20% piperidine in DMF (40 mL) was added and the mixture was bubbled with N2 for 30 min at 25 °C. The mixture was filtered and washed with DMF (20 mL) * 5 before proceeding to next step. 2) Coupling: A solution of Fmoc-Leu-OH (1.06 g, 3.00 mmol, 3.00 equiv.), DIC (378.0 mg, 3.00 mmol, 3.00 equiv.), HOBt (406.0 mg, 3.00 mmol, 3.00 equiv.) in DMF (40 mL) was added to the resin with N2bubbling for 1 h at 25 °C. The coupling reaction was monitored by ninhydrin test. The resin was then washed with DMF (20 mL) * 5.3) Deprotection: 20% piperidine in DMF (40 mL) was added to the resin and the mixture was bubbled with N2 for 30 min at 25 °C. The deprotection reaction was monitored by ninhydrin test. The resin was then washed with DMF (20 mL) * 5. 4) Steps 2 and 3 were repeated for the following amino acids elongation: Number # 2-14, Table 1. 5) After all the steps were completed, the resin was washed with DMF (20 mL) * 5, MeOH (20 mL) * 5, then dried under reduced pressure to afford resin-bound peptide Intermediate 55 (Rink AM resin, 1.00 mmol). Table 1: The list of amino acids and the corresponding reagents used on solid phase peptide synthesis (SPPS).

[0062] Peptide cleavage and cyclization.1) Cleavage solution (TFA / triisopropylsilane (TIS) / H2O, 95 / 2.5 / 2.5, v / v / v, 50 mL) was added to the flask containing the side-chain protected resin-bound peptide Intermediate 55 (Rink AM resin, 1.00 mmol)at 25oC and stirred for 2 h. After filtration, the filtrate was collected. The filtrate was precipitated with cold isopropyl ether (600 mL). After filtration, the solid was washed with isopropyl ether (500 mL) twice, and the crude peptide was dried under reduced pressure for 2 h to afford Intermediate 56 (1.10 g, crude) as a white solid. 2) To a mixture of Intermediate 56 (1.1 g, crude) in HOAc / MeCN / H2O (4 / 3 / 3, v / v / v, 500 mL) was added 0.1 M I2 / AcOH dropwise until a yellow color persisted, then the mixture was stirred at 25oC for 5 min. The mixture was quenched by addition of 0.1 M aq. Na2S2O3dropwise until the yellow color disappeared. After filtration, the filtrate was purified by prep-HPLC (A: 0.075% TFA / H2O, B: MeCN), followed by lyophilization to afford BH0003599 / Compound 1498 (420.0 mg, 95.9% purity, 25.4% yield) as a white solid. LCMS: RT = 1.469 min, MS calcd.: Mav = 1653.02, mass observed: [M + TFA + H]+= 1768.3, [M + H]+= 1654.1, [M + 2H]2+= 827.2, [M + 3H]3+= 551.9.Example 11b. Preparation of BH0003600

[0063] Preparation of BH0003600 / Compound 1499.BH0003600 / Compound 1499 was synthesized by following the procedure of Example 11a, in which SPPS was performed by amino acids elongation shown in Table 2. Table 2: The list of amino acids and the corresponding reagents used on SPPS.BH0003600 / Compound 1499 (380.0 mg, 93.6% purity, 23.8% yield) was afforded as a white solid. LCMS: RT = 1.52 min, MS calcd.: Mav= 1593.99, mass observed: [M + H]+= 1595.1, [M + 2H]2+= 798.2, [M + 3H]3+= 532.2.Example 11c. Preparation of BH0003601

[0064] Preparation of BH0003601 / Compound 1500.BH0003601 / Compound 1500 was synthesized by following the procedure of Example 11a, in which SPPS was performed by amino acids elongation shown in Table 3. Table 3: The list of amino acids and the corresponding reagents used on SPPS.BH0003601 / Compound 1500 (390.0 mg, 97.7% purity, 23.6% yield) was afforded as a white solid. LCMS: RT = 1.444 min, MS calcd.: Mav= 1654.00, mass observed: [M + H]+= 1654.2, [M + 2H]2+= 827.2, [M + 3H]3+= 551.9.Example 11d. Preparation of BH0003620

[0065] Preparation of BH0003620 / Compound 1558. BH0003620 / Compound 1558 was synthesized by following the procedure of Example 11a, in which SPPS was performed by amino acids elongation shown in Table 4. Table 4: The list of amino acids and the corresponding reagents used on SPPS.BH0003620 / Compound 1558 (451.7 mg, 97.4% purity, 23.6% yield) was afforded as a white solid. LCMS: RT = 1.29 min, MS calcd.: Mav= 1668.04, mass observed: [M + H]+= 1669.1, [M + 2H]2+= 835.2, [M + 3H]3+= 557.0.Example 11e. Preparation of BH0003621

[0066] Preparation of BH0003621 / Compound 1559. BH0003621 / Compound 1559 was synthesized by following the procedure of Example 11a, in which SPPS was performed by amino acids elongation shown in Table 5. Table 5: The list of amino acids and the corresponding reagents used on SPPS.BH0003621 / Compound 1559 (399.1 mg, 96.0% purity, 23.9% yield) was afforded as a white solid. LCMS: RT = 1.469 min, MS calcd.: Mav = 1667.05, mass observed: [M + H]+= 1668.2, [M + 2H]2+= 834.3, [M + 3H]3+= 556.5.EXAMPLE 12. Procedure for preparation of BH0003656 / Compound 1480, BH0003598 / Compound 1481, BH0003706 / Compound 1484, BH0003380 / Compound 1433 and BH0003409 / Compound 1353. Example 12a. Preparation of Petide Intermediate 59

[0067] Preparation of Intermediate 57 (sidechain protected resin-bound peptide).SPPS (2.0 mmol loading) was performed by following the procedure of Example 11a with amino acids elongation shown in Table 6. Table 6: The list of amino acids and the corresponding reagents used on SPPS.

[0068] Preparation of Intermediate 59 (cleavage and cyclization).Intermediate 59 was synthesized by following the procedure of Example 11a, which underwent cleavage and subsequent cyclization. Intermediate 59 (800.0 mg, 96.4% purity, 20.4% yield) was afforded as a white solid. LCMS: RT = 0.784 min, MS calcd.: Mav= 1959.36, mass observed: [M + 2H]2+= 980.20, [M + 3H]3+= 653.9.Example 12b. Preparation ofBH0003656

[0069] Preparation of BH0003656 / Compound 1480. To a solution of Intermediate 59 (157.5 mg, 80.4 μmol, 1.05 equiv.) and Target A089 (100.0 mg, 76.6 μmol, 1.00 equiv.) in DMF (1.5 mL) was added CuSO4(0.4 M, 12.2 mg, 76.6 μmol, 1.00 equiv.), Na ascorbate (0.4 M, 37.9 mg, 191.4 μmol, 3.00 equiv.) and THPTA (tris-hydroxypropyltriazolylmethylamine, 33.3 mg, 76.6 μmol, 1.00 equiv.) under nitrogen atmosphere at 0oC, and the resulting mixture was stirred for 3 h at 0oC. After completion monitored by LC-MS, the reaction was filtered off and purified by prep-HPLC (A: 0.075% TFA / H2O; B: MeCN), followed by lyophilization to afford BH0003656 / Compound 1480 (136.5 mg,97.3% purity, 54.6% yield) as a white solid. LCMS: RT = 1.318 min, MS calcd.: Mav= 3265.74, mass observed: [M + 2H]2+= 1634.0, [M + 3H]3+= 1089.5, [M + 4H]4+= 817.4, [M + 5H]5+= 654.2. The full structure of BH0003656 is shown in Figure 1. Example 12c. Preparation of BH0003598

[0070] Preparation of BH0003598 / Compound 1481. BH0003598 / Compound 1481 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A091 and Intermediate 59. White solid, 30.4 mg, 93.1% purity, 43.7% yield. LCMS: RT = 1.323 min, MS calcd.: Mav= 2749.19, mass observed: [2M + 3H]3+= 1833.8, [M + 2H]2+= 1375.5, [M + 3H]3+= 917.2, [M + 4H]4+= 668.2, [M + 5H]5+= 550.7. The full structure of BH0003598 is shown in Figure 2. Example 12d. Preparation of BH0003706

[0071] Preparation of BH0003706 / Compound 1484.Intermediate 59A was synthesized by following the procedure mentioned in Example 12a, the only difference lied in the 7thAmino acid, which was used Fmoc-D-Arg(Pbf)-OH instead of the Fmoc-L-Arg(Pbf)- OH during SPPS. BH0003706 / Compound 1484 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 59a. White solid, 19.6 mg, 96.1% purity, 33.9% yield. LCMS: RT = 1.308 min, MS calcd.: Mav= 3782.28, mass observed: [2M + 3H]3+= 1892.3, [M + 2H]2+= 1261.7, [M + 3H]3+= 946.3, [M + 4H]4+= 757.6, [M + 5H]5+= 631.4. The full structure of BH0003706 is shown in Figure 3. Example 12e. Preparation of BH0003380

[0072] Preparation of BH0003380 / Compound 1433. BH0003380 / Compound 1433 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A044 and Intermediate 59. Target 044 was prepared from Intermediate 20 and Intermediate 40 analogously to the preparation of Target 068 as described in Example 7. BH0003380 / Compound 1433: White solid. 59.2 mg, 95.1% purity, 20.6% yield. LCMS: RT = 1.322 min, MS calcd.: Mav = 3542.0, mass observed: [M + 2H]2+= 1771.9, [M + 3H]3+= 1181.6, [M + 4H]4+= 886.5. The full structure of BH0003380 is shown in Figure 4. Example 12f. Preparation of BH0003409

[0073] Preparation of BH0003409 / Compound 1353. BH0003409 / Compound 1353 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 59. White solid. 40.2 mg, 96.9% purity, 25.6% yield. LCMS: RT = 0.784 min, MS calcd.: Mav= 3782.3, mass observed: [M + 3H]3+= 1261.89, [M + 4H]4+= 946.39, [M + 5H]5+= 757.38. The full structure of BH0003409 is shown in Figure 5.EXAMPLE 13. Procedure for preparation of BH0003707 / Compound 1485.

[0074] Preparation of Intermediate 60. Intermediate 60 was synthesized by following the procedure of Example 11a, in which SPPS (0.3 mmol loading) was performed by amino acids elongation shown in Table 7.0.3 mmol resin afford Intermediate 60 (118.40 mg, 100% purity, 20.0% yield) as a white solid. LCMS: RT = 0.819 min, MS calcd.: Mav = 1973.39, mass observed: [M + 2H]2+= 987.14, [M + 3H]3+= 658.51.Table 7: The list of amino acids and the corresponding reagents used on SPPS.

[0075] Preparation of BH0003707 / Compound 1485.BH0003707 / Compound 1485 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 60. White solid, 12.4 mg, 92.6% purity, 38.1% yield. LCMS: RT = 1.323 min, MS calcd.: Mav = 3796.30, mass observed: [M + 2H]2+= 1899.3, [M + 3H]3+= 1266.7, [M + 4H]4+= 950.0, [M + 5H]5+= 760.4. The full structure of BH0003707 is shown in Figure 6. EXAMPLE 14. Procedure for preparation of BH0003708 / Compound 1486.

[0076] Preparation of Intermediate 61. Intermediate 61 was synthesized by following the procedure of Example 11a, in which SPPS (0.3 mmol loading) was performed by amino acids elongation shown in Table 8.0.3 mmol resin afford Intermediate 61 (125.40 mg, 93.7% purity, 19.4% yield) as a white solid. LCMS: RT = 0.793 min, MS calcd.: M= 2015.47, mass observed: [M + 2H]2+= 1008.20, [M + 3H]3+= 672.53.Table 8: The list of amino acids and the corresponding reagents used on SPPS.

[0077] Preparation of BH0003708 / Compound 1486. BH0003708 / Compound 1486 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 61. White solid, 22.9 mg, 93.8% purity, 41.1% yield. LCMS: RT = 1.308 min, MS calcd.: Mav = 3838.38, mass observed: [M + 2H]2+= 1920.4, [M + 3H]3+= 1280.5, [M + 4H]4+= 960.3, [M + 5H]5+= 768.7. The full structure of BH0003708 is shown in Figure 7. EXAMPLE 15. Procedure for preparation of BH0003709 / Compound 1487.

[0078] Preparation of Intermediate 62. Intermediate 62 was synthesized by following the procedure of Example 11a, in which SPPS (0.3 mmol loading) was performed by amino acids elongation shown in Table 9.0.3 mmol resin afford Intermediate 62 (141.40 mg, 100.0% purity, 29.5% yield) as a white solid. LCMS: RT = 0.863 min, MS calcd.: Mav= 1593.91, mass observed: [M + 2H]2+= 797.5.Table 9: The list of amino acids and the corresponding reagents used on SPPS.

[0079] Preparation of BH0003709 / Compound 1487. BH0003709 / Compound 1487 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 62. White solid, 10.2 mg, 90.3% purity, 30.3% yield. LCMS: RT = 1.341 min, MS calcd.: M = 3416.83, mass observed: [M + 2H]2+= 1709.7, [M + 3H]3+= 1139.6, [M + 4H]4+= 855.1, [M + 5H]5+= 684.1.The full structure of BH0003709 is shown in Figure 8. EXAMPLE 16. Procedure for preparation of BH0003734 / Compound 1488.

[0080] Preparation of Intermediate 63. Intermediate 63 was synthesized by following the procedure of Example 11a, in which SPPS (0.3 mmol loading) was performed by amino acids elongation shown in Table 10. 0.3 mmol resin afforded Intermediate 63 (175.0 mg, 94.1% purity, 35.1% yield) as a white solid. LCMS: RT = 0.907 min, MS calcd.: Mav = 1666.09, mass observed: [M + 2H]2+= 833.56.Table 10: The list of amino acids and the corresponding reagents used on SPPS.

[0081] Preparation of BH0003734 / Compound 1488. BH0003734 / Compound 1488 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 63. White solid, 33.1 mg, 97.4% purity, 45.3% yield. LCMS: RT = 1.369 min, MS calcd.: Mav= 3489.00, mass observed: [M + 2H]2+= 1745.2, [M + 3H]3+= 1164.1, [M + 4H]4+= 873.4, [M + 5H]5+= 698.7. The full structure of BH0003734 is shown in Figure 9. EXAMPLE 17 Procedure for preparation of BH0003735 / Compound 1489.

[0082] Preparation of Intermediate 64. Intermediate 64 was synthesized by following the procedure of Example 11a, in which SPPS (0.3 mmol loading) was performed by amino acids elongation shown in Table 11. 0.3 mmol resin afforded Intermediate 64 (158.1 mg, 80.3% purity, 21.4% yield) as a white solid. LCMS: RT = 0.801 min, MS calcd.: Mav = 1973.39, mass observed: [M + 2H]2+= 987.1, [M + 3H]3+= 658.53.Table 11: The list of amino acids and the corresponding reagents used on SPPS.

[0083] Preparation of BH0003735 / Compound 1489.BH0003735 / Compound 1489 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 64. White solid, 24.1 mg, 96.6% purity, 40.5% yield. LCMS: RT = 1.311 min, MS calcd.: Mav = 3796.31, mass observed: [M + 2H]2+= 1898.8, [M + 3H]3+= 1266.3, [M + 4H]4+= 950.0, [M + 5H]5+= 760.5. The full structure of BH0003735 is shown in Figure 10. EXAMPLE 18. Procedure for preparation of BH0003736 / Compound 1490.

[0084] Preparation of Intermediate 65. Intermediate 65 was synthesized by following the procedure of Example 11a, in which SPPS (0.3 mmol loading) was performed by amino acids elongation shown in Table 12. 0.3 mmol resin afforded Intermediate 65 (250.0 mg, 86.9% purity, 36.9% yield) as a white solid. LCMS: RT = 0.845 min, MS calcd.: Mav = 1959.36, mass observed: [M + 2H]2+= 980.2, [M + 3H]3+= 653.8.Table 12: The list of amino acids and the corresponding reagents used on SPPS.

[0085] Preparation of BH0003736 / Compound 1490. BH0003736 / Compound 1490 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 65. White solid, 21.9 mg, 94.0% purity, 35.2% yield. LCMS: RT = 1.307 min, MS calcd.: Mav = 3782.28, mass observed: [M + 2H]2+= 1892.3, [M + 3H]3+= 1261.7, [M + 4H]4+= 946.5, [M + 5H]5+= 757.4. The full structure of BH0003736 is shown in Figure 11. EXAMPLE 19. Procedure for preparation of BH0003737 / Compound 1491.

[0086] Preparation of Intermediate 66.Intermediate 66 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 13. 0.5 mmol resin afforded Intermediate 66 (326.7 mg, 33.1% yield) as a white solid. LCMS: RT = 0.828 min,= 1973.39, mass observed: [M + 2H]2+= 987.10, [M + 3H]3+= 658.61.Table 13: The list of amino acids and the corresponding reagents used on SPPS.

[0087] Preparation of BH0003737 / Compound 1491. BH0003737 / Compound 1491 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of target A068 and Intermediate 66. White solid, 32.5 mg, 95.7% purity, 52.0% yield. LCMS: RT = 1.322 min, MS calcd.: Mav = 3796.31, mass observed: [M + 2H]2+= 1899.3, [M + 3H]3+= 1266.3, [M + 4H]4+= 950.0, [M + 5H]5+= 760.3. The full structure of BH0003737 is shown in Figure 12. EXAMPLE 20. Procedure for preparation of BH0003776 / Compound 1492.

[0088] Preparation of Intermediate 67. Intermediate 67 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 14. 0.3 mmol resin afforded Intermediate 67 (315.0 mg, 31.7% yield) as a white solid. LCMS: RT = 0.801 min, MS calcd.: Mav= 1987.42, mass observed: [M + 2H]2+= 994.1, [M + 3H]3+= 663.19.Table 14: The list of amino acids and the corresponding reagents used on SPPS.

[0089] Preparation of BH0003776 / Compound 1492.BH0003776 / Compound 1492 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 67. White solid, 16.2 mg, 92.4% purity, 25.8% yield. LCMS: RT = 1.312 min, MS calcd.: Mav = 3810.33, mass observed: [M + 2H]2+= 1906.3, [M + 3H]3+= 1271.1, [M + 4H]4+= 953.4, [M + 5H]5+= 763.0. The full structure of BH0003776 is shown in Figure 13. EXAMPLE 21. Procedure for preparation of BH0003738 / Compound 1493.

[0090] Preparation of Intermediate 68. Intermediate 68 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 15. 0.3 mmol resin afforded Intermediate 68 (328.0 mg, 80.3% purity, 21.4% yield) as a white solid. LCMS: RT = 0.784 min, MS calcd.: Mav= 1987.42, mass observed: [M + 2H]2+= 994.2, [M + 3H]3+= 663.2.Table 15: The list of amino acids and the corresponding reagents used on SPPS.

[0091] Preparation of BH0003738 / Compound 1493. BH0003738 / Compound 1493 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 68. White solid, 27.1 mg, 96.9% purity, 43.2% yield. LCMS: RT = 1.285 min, MS calcd.: Mav = 3810.33, mass observed: [M + 2H]2+= 1906.3, [M + 3H]3+= 1271.0, [M + 4H]4+= 953.4, [M + 5H]5+= 762.9. The full structure of BH0003738 is shown in Figure 14. EXAMPLE 22. Procedure for preparation of BH0003739 / Compound 1494.

[0092] Preparation of Intermediate 69.Intermediate 69 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 16. 0.3 mmol resin afforded Intermediate 69 (350.0 mg, 35.4% yield) as a white solid. LCMS: RT = 0.713 min,= 1974.38, mass observed: [M + 2H]2+= 987.61, [M + 3H]3+= 658.87.Table 16: The list of amino acids and the corresponding reagents used on SPPS.

[0093] Preparation of BH0003739 / Compound 1494. BH0003739 / Compound 1494 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 69. White solid, 18.3 mg, 92.3% purity, 22.0% yield. LCMS: RT = 1.218 min, MS calcd.: Mav = 3797.29, mass observed: [M + 2H]2+= 1900.2, [M + 3H]3+= 1266.6, [M + 4H]4+= 950.4, [M + 5H]5+= 760.4. The full structure of BH0003739 is shown in Figure 15. EXAMPLE 23. Procedure for preparation of BH0003740 / Compound 1495.

[0094] Preparation of Intermediate 70. Intermediate 70 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 17. 0.5 mmol resin afforded Intermediate 70 (305.0 mg, 80.3% purity, 30.9% yield) as a white solid. LCMS: RT = 0.810 min, MS calcd.: Mav= 1973.39, mass observed: [M + 2H]2+= 987.19, [M + 3H]3+= 658.56.Table 17: The list of amino acids and the corresponding reagents used on SPPS.

[0095] Preparation of BH0003740 / Compound 1495.BH0003740 / Compound 1495 was synthesized by following the procedure mentioned in step 2) of Example 12b mutatis mutandiswith the treatment of target A068 and Intermediate 70. White solid, 46.5 mg, 96.1% purity, 55.8% yield. LCMS: RT = 1.322 min, MS calcd.: Mav = 3796.31, mass observed: [M + 2H]2+= 1899.3, [M + 3H]3+= 1266.4, [M + 4H]4+= 949.9, [M + 5H]5+= 760.1. The full structure of BH0003740 is shown in Figure 16. EXAMPLE 24. Procedure for preparation of BH0003741 / Compound 1496.

[0096] Preparation of Intermediate 71. Intermediate 71 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 18. 0.5 mmol resin afforded Intermediate 71 (158.1 mg, 80.3% purity, 21.4% yield) as a white solid. LCMS: RT = 0.819 min, MS calcd.: Mav = 1959.36, mass observed: [M + 2H]2+= 980.15, [M + 3H]3+= 658.8.Table 18: The list of amino acids and the corresponding reagents used on SPPS.

[0097] Preparation of BH0003741 / Compound 1496.BH0003741 / Compound 1496 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 71. White solid, 36.2 mg, 97.4% purity, 43.6% yield. LCMS: RT = 1.307 min, MS calcd.: Mav = 3782.28, mass observed: [M + 2H]2+= 1891.8, [M + 3H]3+= 1261.5, [M + 4H]4+= 946.7, [M + 5H]5+= 757.5. The full structure of BH0003741 is shown in Figure 17. EXAMPLE 25. Procedure for preparation of BH0003777 / Compound 1497.

[0098] Preparation of Intermediate 72. Intermediate 72 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 19. 0.5 mmol resin afforded Intermediate 72 (297.0 mg, 30.2% yield) as a white solid. LCMS: RT = 0.845 min, MS calcd.: Mav = 1965.41, mass observed: [M + 2H]2+= 983.15, [M + 3H]3+= 655.88.Table 19: The list of amino acids and the corresponding reagents used on SPPS.

[0099] Preparation of BH0003777 / Compound 1497.BH0003777 / Compound 1497 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of target A068 and Intermediate 72. White solid, 18.1 mg, 95.9% purity, 43.5% yield. LCMS: RT = 1.362 min, MS calcd.: Mav = 3788.33, mass observed: [M + 2H]2+= 1894.8, [M + 3H]3+= 1263.9, [M + 4H]4+= 948.0, [M + 5H]5+= 758.6. The full structure of BH0003777 is shown in Figure 18. EXAMPLE 26. Procedure for preparation of BH0003742 / Compound 1501 (Comparative example).

[0100] Preparation of Intermediate 73. Intermediate 73 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 20. 0.5 mmol resin afforded Intermediate 73 (380.0 mg, 21.4% yield) as a white solid. LCMS: RT = 0.863 min,= 1747.13, mass observed: [M + 2H]2+= 874.1.Table 20: The list of amino acids and the corresponding reagents used on SPPS.

[0101] Preparation of BH0003742 / Compound 1501. BH0003742 / Compound 1501 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of target A068 and Intermediate 73. White solid, 20.4 mg, 98.5% purity,34.7% yield. LCMS: RT = 1.358 min, MS calcd.: = 3570.05, mass observed: [M + 2H]2+= 1786.3, [M + 3H]3+= 1191.1, [M + 4H]4+= 893.5, [M + 5H]5+= 714.9. The full structure of BH0003742 is shown in Figure 19. EXAMPLE 27. Procedure for preparation of BH0003743 / Compound 1502 (Comparative example).

[0102] Preparation of Intermediate 74. Intermediate 74 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 21. 0.5 mmol resin afforded Intermediate 74 (158.1 mg, 80.3% purity, 21.4% yield) as a white solid. LCMS: RT = 0.925 min, MS calcd.: Mav = 1688.11, mass observed: [M + 2H]2+= 844.6, [M + 3H]3+= 563.5.Table 21: The list of amino acids and the corresponding reagents used on SPPS.

[0103] Preparation of BH0003743 / Compound 1502. BH0003743 / Compound 1502 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 74. White solid, 24.1 mg, 96.1% purity, 41.7% yield. LCMS: RT = 1.390 min, MS calcd.: Mav= 3511.03, mass observed: [M + 2H]2+= 1756.7, [M + 3H]3+= 1171.3, [M + 4H]4+= 878.7, [M + 5H]5+= 703.2. The full structure of BH0003743 is shown in Figure 20. EXAMPLE 28. Procedure for preparation of BH0003744 / Compound 1503.

[0104] Preparation of Intermediate 75. Intermediate 75 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 22. 0.5 mmol resin afforded Intermediate 75 (200.0 mg, 22.8% yield) as a white solid. LCMS: RT = 0.854 min, MS calcd.: Mav= 1973.39, mass observed: [M + 2H]2+= 874.08.Table 22: The list of amino acids and the corresponding reagents used on SPPS.

[0105] Preparation of BH0003744 / Compound 1503. BH0003744 / Compound 1503 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 75. White solid, 45.1 mg, 98.8% purity,57.6% yield. LCMS: RT = 1.335 min, MS calcd.: = 3570.05, mass observed: [M + 2H]2+= 1785.8, [M + 3H]3+= 1190.8, [M + 4H]4+= 893.4, [M + 5H]5+= 715.0. The full structure of BH0003744 is shown in Figure 21. EXAMPLE 29. Procedure for preparation of BH0003745 / Compound 1560 (Comparative example).

[0106] Preparation of Intermediate 76. Intermediate 76 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 23. 0.5 mmol resin afforded Intermediate 76 (310.0 mg, 80.3% purity, 35.1% yield) as a white solid. LCMS: RT = 0.749 min, MS calcd.: Mav= 1762.15, mass observed: [M + 2H]2+= 881.56, [M + 3H]3+= 588.13.Table 23: The list of amino acids and the corresponding reagents used on SPPS.

[0107] Preparation of BH0003745 / Compound 1560. BH0003745 / Compound 1560 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 76. White solid, 28.5 mg, 95.3% purity, 36.2% yield. LCMS: RT = 1.227 min, MS calcd.: Mav = 3585.06, mass observed: [M + 2H]2+= 1793.3, [M + 3H]3+= 1195.8, [M + 4H]4+= 897.3, [M + 5H]5+= 718.1 The full structure of BH0003745 is shown in Figure 22. EXAMPLE 30. Procedure for preparation of BH0003778 / Compound 1561.

[0108] Preparation of Intermediate 77. Intermediate 77 was synthesized by following the procedure of Example 11a, in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 24. 0.5 mmol resin afforded Intermediate 77 (310.0 mg, 35.2% yield) as a white solid. LCMS: RT = 0.872 min, MS calcd.: Mav= 1761.16, mass observed: [M + 2H]2+= 881.1.Table 24: The list of amino acids and the corresponding reagents used on SPPS.

[0109] Preparation of BH0003778 / Compound 1561. BH0003778 / Compound 1561 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Target A068 and Intermediate 77. White solid, 53.5 mg, 98.5% purity,68.0% yield. LCMS: RT = 1.365 min, MS calcd.: Mav= 3584.08, mass observed: [M + 2H]2+= 1793.3, [M + 3H]3+= 1195.6, [M + 4H]4+= 897.0, [M + 5H]5+= 717.7. The full structure of BH0003778 is shown in Figure 23. EXAMPLE 31. Procedure for preparation of BH0003592 / Compound 1539.

[0110] Preparation of Intermediate 79.To a solution of 78 (500.0 mg, 2.46 mmol, 1.00 equiv.) in DMF (2 mL) was added TFP (tetrafluorophenol, 817.5 mg, 4.92 mmol, 2.00 equiv.) and EDCI (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide, 704.6 mg, 3.69 mmol, 1.50 equiv.). The reaction was stirred at 25 °C for 16 h. After completion monitored by LC-MS, the mixture was purified by prep-HPLC (A: 0.075% TFA / H2O, B: MeCN) to afford Intermediate 79 (360.0 mg, 1.03 mmol, 41.7% yield) as yellow oil. LCMS: RT = 1.152 min, MS calcd.: Mav = 351.25, mass observed: [M – N2 + H]+= 324.10.

[0111] Preparation of Intermediate 80.To a solution of Target A073 (10.0 mg, 6.44 μmol, 1.00 equiv.) and Intermediate 79 (9.0 mg, 25.8 μmol, 4.0 equiv.) in DMF (1 mL) was added DIEA (1.66 mg, 12.87 μmol, 2.24 μL, 2.00 equiv.), and the resulting mixture was stirred at 25 °C for 1 h. After completion monitored by LC-MS, the mixture was purified by prep-flash column (A: 0.075% TFA / H2O; B: MeCN) to afford Intermediate 80 (2.4 mg, 20.8% yield) as a white solid.

[0112] Preparation of BH0003592 / Compound 1539.BH0003592 / Compound 1539 was synthesized by following the procedure of Example 12b mutatis mutandis with the treatment of Intermediate 59 and Intermediate 80. White solid, 2.0 mg, 94.0% purity, 44.1% yield. LCMS: RT = 1.525 min, MS calcd.: Mav= 3698.25, mass observed: [M + 2H]2+= 1850.4, [M + 3H]3+= 1233.7, [M + 4H]4+= 925.6, [M + 5H]5+= 740.7, [M + 6H]6+= 617.4. The full structure of BH0003592 is shown in Figure 24. EXAMPLE 32. Procedure for preparation of BH0003658 / Compound 1483. EXAMPLE 32a. Intermediate 81B

[0113] Preparation of Intermediate 81B (resin-bound peptide).Intermediate 81B was synthesized by following the procedure of Example 11a in which SPPS (0.5 mmol loading) was performed by amino acids elongation shown in Table 25. Table 25: The list of amino acids and the corresponding reagents used on SPPS.

[0114] Preparation of Intermediate 82.Intermediate 82 was synthesized by following the procedure mentioned in section

[0062] , which underwent cleavage and subsequent cyclization. Intermediate 82 (120.0 mg, 96.4% purity, 20.4% yield) was afforded as a white solid. EXAMPLE 32b. BH0003658

[0115] Preparation of BH0003658 / Compound 1483.To a solution of Target A011A (30.0 mg, 18.3 μmol, 1.00 equiv.) and Intermediate 82 (64.4 mg, 29.3 μmol, 1.60 equiv.) in DMF (0.2 mL) was added DIEA (12.5 μL, 73.2 μmol, 4.00 equiv.), and the resulting mixture was stirred at 25 °C for 1 h. After completion monitored by LC-MS, the reaction was filtered off and the residue was purified by prep-HPLC (A: 0.075% TFA / H2O; B: MeCN), followed by lyophilization to afford BH0003658 / Compound 1483 (22.4 mg, 88.7% purity, 33.3% yield) as a white solid. LCMS: RT = 1.323 min, MS calcd.: Mav = 3670.19, mass observed: [M + 3H]3+= 1224.0, [M + 4H]4+= 918.2, [M + 5H]5+= 734.8. The full structure of BH0003658 is shown in Figure 25. EXAMPLE 33. Procedure for preparation of BH0003596 / Compound 1473 and BH0003597 / Compound 1478. EXAMPLE 33a. Intermediate 83

[0116] Preparation of Intermediate 83.A mixture of Target A011A (90.0 mg, 55.0 μmol, 1.00 equiv.), Bicyclo[6.1.0]non-4-yn-9-ylmethyl (2,5- dioxopyrrolidin-1-yl) carbonate (BCN-OSu, 24.0 mg, 82.5 μmol, 1.50 equiv.), DIEA (37.5 μL, 220.0 μmol, 4.00 equiv.) in DMF (1.0 mL) was stirred at 25 °C for 1 h. The mixture was purified by prep-HPLC (A: 0.075% TFA / H2O, B: MeCN) directly to afford Intermediate 83 (27.0 mg, 25.7% yield) as a white solid. LCMS: RT = 0.793 min, MS cal.: 1813.94, mass observed: [M + 2H]2+= 907.58, [M + 2H]2+= 605.36. EXAMPLE 33b. Intermediate 84

[0117] Preparation of Intermediate 84.

[0118] Peptide was synthesized using standard Fmoc chemistry (CTC resin). 1) Resin preparation: To the vessel containing CTC resin (1.00 g, 1.00 mmol, 1.00 mmol / g) and Fmoc- Lys(Boc)-OH (468.5 mg, 1.00 mmol, 1.00 equiv.) in DCM (10 mL) was added DIEA (4.00 equiv.) dropwise and mixed for 2 h with N2 bubbling at 25 °C. Then MeOH (1.0 mL) was added and bubbled with N2 for another 30 min. The resin was washed with DMF (20 mL) * 5, followed by the addition of 20% piperidine in DMF (10 mL) and bubbled with N2 for 30 min at 25 °C for Fmoc deprotection. The mixture was filtered and the resin was washed with DMF (10 mL) * 5 before proceeding to next step. 2) Coupling: A solution of Fmoc-Pro-OH (1.01 g, 3.0 mmol, 3.00 equiv.), HBTU (0.82 g, 2.86 mmol, 2.85 equiv.) in DMF (10 mL) was added to the resin with N2bubbling. Then DIEA (6.00 equiv.) was added to the mixture dropwise and bubbled with N2for 30 min at 25 °C. The coupling reaction was monitored by ninhydrin test, if it showed colorless, the coupling was completed. The resin was then washed with DMF (20 mL) * 5. 3) Deprotection: 20% piperidine in DMF (20 mL) was added to the resin and the mixture was bubbled with N2for 30 min at 25 °C. The deprotection reaction was monitored by ninhydrin test, if it showed blue or brownish red, the reaction was completed. The resin was then washed with DMF (20 mL) * 5. 4) Steps 2 and 3 were repeated for the following amino acids elongation: Number # 3-60, Table 26.5) After all the steps were completed, the resin was washed with DMF (50 mL) * 5, MeOH (50 mL) * 5, then dried under reduced pressure to afford resin-bound peptide (CTC resin, 1.00 mmol). Table 26: The list of amino acids and the corresponding reagents used on SPPS.

[0119] Peptide cleavage: A solution of TFA / TIS / H2O / 3-mercaptopropanoic acid (92.5 / 2.5 / 2.5 / 2.5, v / v / v, 40 mL) was added to the resin-bound peptide above at room temperature and stirred for 2 h. After filtration, the filtrate was collected and precipitated with cold isopropyl ether (200 mL), then filtered off, and the solid was washed with isopropyl ether (100 mL) twice, and the crude peptide was dried under reduced pressure for 2 h to afford Intermediate 84 (0.50 mmol, crude) as a white solid. EXAMPLE 33c. BH0003596

[0120] Preparation of BH0003596 / Compound 1473. A mixture of Intermediate 83 (26.0 mg, 14.3 μmol, 1.10 equiv.) and Intermediate 84 (86.5 mg, 13.0 μmol, 1.00 equiv.) in DMF (1.0 mL) was stirred at 25 °C for 12 h. After completion monitored by LC-MS, the mixture was purified by prep-HPLC (A: 0.075% TFA / H2O, B: MeCN) directly to afford BH0003596 / Compound 1473 (76.0 mg, 96.2% purity, 66.4% yield) as a white solid. LCMS: RT = 1.536 min, MS calcd.: M = 8455.37, mass observed: [M + 5H]5+= 1692.6, [M + 6H]6+= 1410.4, [M + 7H]7+= 1208.7, [M + 8H]8+= 1058.1, [M + 9H]9+= 940.4, [M + 10H]10+= 846.3, [M + 11H]11+= 769.4, [M + 12H]12+= 705.9.Partial structure 1:Partial structure 3:BH0003596 has the same peptide sequence as Intermediate 84. *, **, *** and ****, respectively mark the common bonds between the five partial structures of BH0003596 shown above. The combination of the four partial structures discloses the full structure of BH0003596. The full structure of BH0003596 is also shown in Figure 26. EXAMPLE 33d. BH0003597

[0121] Preparation of BH0003597 / Compound 1478.Intermediate 85 was synthesized by following the procedure mentioned in Example 33a with the treatment of Target A001A. (60.0 mg, 96.2% purity, 53.4% yield) was afforded as a white solid. LCMS: RT = 0.687 min, MS calcd.: Mav = 1573.68, mass observed: [M + 2H]2+= 787.52. Compound 1478 was synthesized by following the procedure mentioned in Example 33c with the treatment of Intermediate 84 and Intermediate 85. BH0003597 / Compound 1478 (135.1 mg, 96.9% purity, 45.6% yield) was afforded as a white solid. LCMS: RT = 1.499 min, MS calcd.: Mav= 8215.10, mass observed:[M + 5H]5+= 1644.0, [M + 6H]6+= 1370.2, [M + 7H]7+= 1174.6, [M – 203 + 7H]7+= 1145.7, [M + 8H]8+= 1027.9, [M – 203 + 8H]8+= 1102.5, [M + 9H]9+= 914.0, [M -203 + 9H]9+= 891.4, [M + 10H]10+= 822.7, [M + 11H]11+= 748.3. Partial structure 1:Partial structure 3:*, **, *** and ****, respectively mark the common bonds between the four partial structures of BH0003597 shown above.BH0003597 has the same peptide sequence as Intermediate 84 and BH0003596. Partial structures 2 to 4 of BH0003597 are identical to partial structures 2 to 4 of BH0003596. The combination of the four partial structures discloses the full structure of BH0003597. The full structure of BH0003597 is also shown in Figure 27. EXAMPLE 34. Procedure for preparation of BH0003026 / Compound 1121.

[0122] Preparation of Intermediate 87.To a solution of commercially available material 86 (3.00 g, 10.19 mmol, 1.00 equiv.) in DMF (40 mL) was added TFP (14.20 g, 61.16 mmol, 6.00 equiv.) and EDCI (5.86 g, 30.58 mmol, 3.00 equiv.), then the reaction mixture was stirred at 20 °C for 16 h. The mixture was purified by prep-HPLC (A: 0.075% TFA in H2O, B: MeCN) to afford Intermediate 87 (1.89 mg, 90% purity, 31.4% yield) as colorless oil. LCMS: RT = 1.295 min, MS cal.: 590.41, mass observed: [M + H]+= 591.1, [M + Na]+= 613.2.

[0123] Preparation of Intermediate 88.To a solution of Intermediate 87 (166.24 mg, 281.56 μmol, 5.00 equiv.) in DMF (0.5 mL) was added a mixture of Intermediate 40 (100.0 mg, 56.31 μmol, 1.00 equiv.) and DIEA (36.3 mg, 281.56 μmol, 49.04 μL, 5.00 equiv.) in DMF (1 mL). Then the reaction mixture was stirred at 0 °C for 5 min. The mixture was purified by prep-HPLC (A: 0.075% TFA in H2O, B: MeCN) to afford Intermediate 88 (51.0 mg, 90% purity, 41.2% yield) as a white solid. LCMS: RT = 0.942 min, MS cal.: 2200.14, mass observed: [M + 2H]2+= 1100.6.

[0124] Preparation of Intermediate 89.SPPS was performed by following the procedure mentioned in Example 33b with amino acids elongation shown in Table 27. Table 27: The list of amino acids and the corresponding reagents used on SPPS.Cleavage and cyclization were performed by following the procedure mentioned in section

[0062] . Intermediate 89 (380.0 mg, 93.6% purity, 23.8% yield) was afforded as a white solid.

[0125] Preparation of Intermediate 90.To a solution of Intermediate 88 (50.0 mg, 22.73 μmol, 1.00 equiv.) in DMF (0.5 mL) was added Intermediate 89 (42.0 mg, 22.73 μmol, 1.00 equiv.) and DIEA (5.87 mg, 45.45 μmol, 7.92 μL, 2.00 equiv.). Then the reaction mixture was stirred at 0 °C for 1 h. The mixture was purified by prep-HPLC (A: 0.075% TFA in H2O, B: MeCN) to afford Intermediate 90 (19.4 mg, 96.9% purity, 22.0% yield) as a white solid. LCMS: RT = 0.837 min, MS calcd.: Mav = 3885.19, mass observed: [M + 3H]3+= 1295.46, [M + 4H]4+= 971.94.

[0126] * marks the common bond between the two partial structures of Intermediate 90 shown above.Preparation of BH0003026 / Compound 1121.To a solution of Intermediate 90 (19.4 mg, 4.99 μmol, 1.00 equiv.) in THF / H2O (v / v, 1 / 2, 0.6 mL) was added LiOH (0.96 mg, 40.0 μmol, 8.00 equiv.), and the resulting mixture was stirred at 25 °C for 1 h. After completion monitored by LC-MS, the mixture was filtered off and the residue was purified by prep-HPLC (A: 0.075% TFA / H2O, B: MeCN) directly to afford BH0003026 / Compound 1121 (9.6 mg, 96.5% purity, 54.8% yield) as a white solid. LCMS: RT = 10.8 min, MS calcd.: Mav= 3506.8, mass observed: [M + 2H]2+= 1573.54, [M + 3H]3+= 1169.36, [M + 4H]4+= 877.27, [M + 5H]5+= 701.82. ...

Claims

What is claimed is:

1. A compound of Formula (I) or Formula (II), or a pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof, having the structure A-L1-AG Formula (I) A-L1-Con(L2-AG)nFormula (II), wherein A is a protein that is a binding moiety and selected from the group consisting of a BM1, BM2, BM3 and BM4, wherein BM1 is a binding moiety that binds to the hinge region of galactose deficient IgA1 antibodies and has an amino acid sequence at least 80% homologous to SEQ ID NO: 1: HMVC#LSYRGRPVC#FSL, wherein # marks a disulfide bridge between the two L-cysteine rests, BM2 is a binding moiety that binds to the hinge region of galactose deficient IgA1 antibodies and has an amino acid sequence at least 80% homologous to SEQ ID NO: 2: VDNKFNKETIQASQEIRLLPNLNGRQKLAFIHSLLDDPSQSANLLAEAKKLNDAQAPK BM3 is a binding moiety that binds tothe Fc region of IgA1 antibodies and has an amino acid sequence at least 75% homologous to SEQ ID NO: 3: VPS-(Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-P-(Ser-Alpha-GalNAc)-P-(Ser- Alpha-GalNAc)-(Thr-Alpha-GalNAc)-PP-(Thr-Alpha-GalNAc)-PSPS, wherein GalNAc refers to N-acetylgalactosamine, and BM4 is a binding moiety that binds to autoantibodies of galactose deficient IgA1 antibodies and has an amino acid sequence that differs no more than by one amino acid from SEQ ID NO: 26 Gly-Gly-PS-(Thr-Alpha-GalNAc)-PPor from SEQ ID NO: 27: PS-(Thr-Alpha-GalNAc)-PP, wherein GalNAc refers to N-acetylgalactosamine; L1and L2are linker and all linker L1and L2may be the same or different and all occurrences of L2in Formula (II) may be the same or different and L1and L2may also be a direct bond; Con is a connector that is covalently bonded to an open valence of linker L1and to an open valence of each linker L2; n is an integer of 2 or 3 and AG is an asiaglycoprotein receptor binding moiety (ASGPR binding moiety) and each occurrence of AG in Formula (II) may be the same of different.

2. The compound of claim 1, wherein A is BM1.

3. The compound of any of the preceding claims, wherein A is BM1 and BM1 is selected from the group consisting of SEQ ID NO: 1 and amino acid sequences that differ from SEQ ID NO: 1 only in that one or more amino acids of SEQ ID NO: 1 selected from the group consisting of cysteine, leucine, arginine, methionine, serine and phenylalanine are substituted, and if substituted, cysteine is substituted by S-penicillamine, leucine is substituted by N-methyl leucine, arginine is substituted by N- methyl arginine, methionine is substituted by N-methyl methionine, serine is substituted by N-methyl serine and phenylalanine is substituted by 3-hexyl alanine.

4. The compound of any of the preceding claims, wherein A is BM1 and BM1 is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 4 to SEQ ID NO:

10.

5. The compound of any of the preceding claims, wherein A is BM1 and BM1 is SEQ ID NO: 4.

6. The compound of any of claim 1, wherein A is BM2.

7. The compound of claim 6, wherein BM2 is selected from the group consisting of SEQ ID NO: 2 and amino acid sequences that differ from SEQ ID NO: 2 only in that one or more amino acids of SEQ ID NO: 2 selected from the group consisting of leucine, arginine, serine and phenylalanine are substituted, and if substituted, leucine is substituted by N-methyl leucine, arginine is substituted by N-methyl arginine, serine is substituted by N-methyl serine and phenylalanine is substituted by 3-hexyl alanine.

8. The compound of any of claim 6 and 7, wherein BM2 is SEQ ID NO:

2.

9. The compound of claim 1, wherein A is BM3.

10. The compound of claim 9, wherein BM3 is selected from the group consisting of SEQ ID NO: 3 and amino acid sequences that differ from SEQ ID NO: 3 only in that one or more amino acids of SEQ ID NO: 3 selected from the group consisting of serine, threonine, Ser-Alpha-GalNAc, Thr-Alpha-GalNAc are substituted, and if substituted, serine is substituted by Ser-Alpha-GalNAc, threonine is substituted by Thr-Alpha-GalNAc, Ser-Alpha-GalNAc is substituted by serine and Thr-Alpha-GalNAc is substituted by threonine.

11. The compound of any of claims 9 and 10, wherein BM3 is SEQ ID NO:

3.

12. The compound of any of the preceding claims, wherein L1has the structure –(XG)n–, wherein n is an integer from 1 to 105; L2has the structure –(XG)p–, wherein p is an integer from 1 to 50; wherein each occurrence of XG is independently selected from the group consisting of –CH2-, –CH(CH2– OCH3)– ,–CH(CH2–OCH2CH3)–, -C(=O)-, -NH-, –O-, –S(=O)2-, –P(=O)2- and an optionally substituteddivalent cyclic group with 3 to 20 ring atoms, with the proviso that in linker L1and L2no two oxygen atoms are adjacent to each other and L2may also be a direct bond between Con and AG.

13. The compound of any of the preceding claims, wherein the linker L1and L2do not comprise carboxyl ester groups.

14. The compound of any of the preceding claims, wherein L1and L2are copolymers with a chain length of 3 to 50 atoms, comprising one or more of –(CH2)y–, wherein Y is an integer in the range of 1 to 5, and one of the hydrogen atoms in each –CH2- residue may be substituted by a residue selected from the group consisting of a halogen atom or a residue –CH2-O-CH3or –CH2-O-CH2-CH3, and wherein a plurality of –(CH2)y– moieties are bonded to each other by a residue selected from the group consisting of –O–, –CONH–, –NHCONH–, –SO2-NH–, -PO2-NH– and an optionally substituted divalent cyclic group with 3 to 20 ring atoms.

15. The compound of claim14, wherein Y is an integer in the range of 1 to 4, preferably 1 to 3.

16. The compound of any of the preceding claims, wherein L1and L2are copolymers comprising repeating units selected from the group consisting of –CH2-, -NH-, –CH2-O-, –(CH2CH2-O)-, –(CH2-NH)-, – (CH2CH2-NH)-, –(CH2CH2CH2-NH)-, -CH2C(=O)-, -CH2CH2C(=O)-, -CH2CH2CH2C(=O)-, -C(=O)CH2CH2C(=O)-, - C(=O)CH2CH2CH2C(=O)-, C(=O)CH2CH2CH2CH2C(=O)-and an optionally substituted divalent cyclic group with 3 to 20 ring atoms.

17. The compound of any of claims 14 to 16, wherein L1and L2consist of the repeating units.

18. The compound of any of claims 12 to 17, wherein the optionally substituted divalent cyclic group with 3 to 20 ring atoms is selected from the group consisting of optionally substituted divalent non-aromatic cyclic group with 3 to 20 ring atoms and optionally substituted divalent aromatic cyclic group with 5 or 6 ring atoms.

19. The compound of any of claims 12 to 18, wherein the optionally substituted divalent cyclic group with 3 to 20 ring atoms comprises an aromatic 5-membered heterocycle selected from the group consisting pyrroles, furans, thiophens, pyrazoles, oxazoles, isoxazoles, thiazoles, isothiazoles, triazoles, furazans, oxadiazoles, thiadiazoles and tetrazoles.

20. The compound of any of claims 12 to 19, wherein the optionally substituted divalent cyclic group with 3 to 20 ring atoms comprises a 1H-1,2,3-triazole ring and preferably is selected from the group consisting of 1H-1,2,3-triazole, which is preferably bound to the remainder of the molecule in 1- and 4-position,, wherein * marks the open valences with which the group is bound to the remainder of the molecule.

21. The compound of any of claims 12 to 20, wherein the divalent cyclic group with 3 to 20 ring atoms is not substituted.

22. The compound of any of the preceding claims, wherein at least one of L1and L2is selected from the group consisting of (1): -C(=O)CH2CH2C(=O)-NH-(CH2CH2-O)3-CH2CH2C(=O)-NH-CH2C(=O)-NH-, (2): –CH2-O-CH2CH2-O-CH2CH2C(=O)-NH-CH2C(=O)-NH-, (3): –CH2-O-(CH2CH2-O)3-CH2CH2C(=O)-NH-CH2C(=O)-NH-, (4): -CH2CH2CH2C(=O)-NHCH2C(O)-NH-,(5): –CH2-O-(CH2CH2-O)3-, (6): –NH-C(=O)-CH2-O-CH2CH2-O-CH2C(=O)-NH-,or wherein L2is a direct bond.

23. The compound of claim 22, wherein L1is selected from the group consisting of linkers (7) to (18).

24. The compound of any of claims 22 or 23, wherein L2is selected from the group consisting of linkers (19), (20) and a direct bond.

25. The compound of any of the preceding claims, wherein AG is selected from the group consisting of monosaccharides, disaccharides, oligosaccharides of up to 20 monosaccharides and derivatives thereof.

26. The compound of any of the preceding claims, wherein AG is a monosaccharide selected from the group consisting of aldoses, aldotetroses, aldopentoses, aldohexoses, ketotrioses, ketotetroses, ketopentose, ketohexoses, aminosugars, sulfosugars, sedoheptulose and sedoheptulose anhydride.

27. The compound of any of the preceding claims, wherein AG is a disaccharide selected from the group consisting of sucrose, lactose, maltose, trehalose, cellobiose, kojibiose, nigerose, isomaltose, β,β- trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiluose, mannobiose, melibiose, melibiulose, rutinose, rutinulose and xylobiose.

28. The compound of any of the preceding claims, wherein AG is selected from the group consisting ofFormula AG-1, Formula AG-2,Formula AG-7, Formula AG-8,Formula AG-11 and Formula AG-12 wherein T is selected from the group consisting of a direct bond and O and U is selected from the group consisting of a direct bond, O and O-CH2, wherein if U is O-CH2, the carbon atom of O-CH2is bound to the C5-atom of the sugar ring moiety and wherein * marks the bond that bounds AG to the remainder of the compounds, with the proviso that no oxygen-oxygen bond is formed between AG and the remainder of the compounds of the present invention; and wherein X1is 1 to 5 contiguous atoms independently selected from O, S, N(R6), and C(R4)(R4), wherein if X1is 1 atom then X1is O, S, N(R6), or C(R4)(R4), if X1is 2 atoms then no more than 1 atom of X1is O, S, or N(R6), if X1is 3, 4, or 5 atoms then no more than 2 atoms of X1are O, S, or N(R6), wherein preferably no two oxygen atoms are adjacent to each other; R is selected from the group consisting of H, or C1-C3alkyl optionally substituted with 1-3 hydroxyl groups; R1is selected from the group consisting of hydrogen, hydroxyl, F, Cl, Br, I, -CN, -N3, alkyl optionally substituted with 1, 2, 3, or 4 substituents, C1-C6-alkyl-CN optionally substituted with 1, 2, 3, or 4 substituents, alkenyl optionally substituted with 1, 2, 3, or 4 substituents, alkynyl optionally substituted with 1, 2, 3, or 4 substituents, haloalkyl optionally substituted with 1, 2, 3, or 4 substituents, aryl optionally substituted with 1, 2, 3, or 4 substituents, arylalkyl optionally substituted with 1, 2, 3, or 4 substituents, heteroaryl optionally substituted with 1, 2, 3, or 4 substituents, heteroaryl alkyl optionally substituted with 1, 2, 3, or 4 substituents, heterocycle optionally substituted with 1, 2, 3, or 4 substituents, heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents, alkoxy optionally substituted with 1, 2, 3, or 4 substituents, haloalkoxy optionally substituted with 1, 2, 3, or 4 substituents, -O-alkenyl, -O-alkynyl, -OR6, C1-C6-alkyl-OR6, -SR6, C1-C6alkyl-SR6, -NR6R7, C0-C6alkyl-NR6R7, - C(O)R3, C0-C6alkyl-C(O)R3, -S(O)R3, C1-C6alkyl-S(O)R3, -C(S)R3, C1-C6alkyl-C(S)R3, -S(O)2R3, C1-C6alkyl-S(O)2R3, -N(R8)-C(O)R3, C1-C6alkyl-N(R8)-C(O)R3, -N(R8)-S(O)R3, C1-C6alkyl-N(R8)-S(O)R3, -N(R8)-C(S)R3, C1-C6alkyl- N(R8)-C(S)R3, -N(R8)-S(O)2R3, C1-C6alkyl-N(R8)-S(O)2R3, -O-C(O)R3, C1-C6alkyl-O-C(O)R3, -O-S(O)R3, C1- C6alkyl-O-S(O)R3, -O-C(S)R3, C1-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C1-C6alkyl-N3, -O-S(O)2R3, or C0-C6alkyl-O- S(O)2R3, each of which is optionally substituted with 1, 2, 3, or 4 substituents; R2is selected from the group consisting of hydrogen, optionally substituted amino, alkyl optionally substituted with 1, 2, 3, or 4 substituents, alkenyl optionally substituted with 1, 2, 3, or 4substituents, allyl optionally substituted with 1, 2, 3, or 4 substituents, alkynyl optionally substituted with 1, 2, 3, or 4 substituents, aryl optionally substituted with 1, 2, 3, or 4 substituents, a heterocycle optionally substituted with 1, 2, 3, or 4 substituents, heteroaryl containing 1, 2 or 3 heteroatoms in the ring which are independently selected from N, O, and S and wherein the heteroaryl groups are optionally substituted with 1, 2, 3, or 4 substituents, R10, alkoxy optionally substituted with 1, 2, 3, or 4 substituents, -O-alkenyl optionally substituted with 1, 2, 3, or 4 substituents, -O-alkynyl optionally substituted with 1, 2, 3, or 4 substituents, -O-aryl optionally substituted with 1, 2, 3, or 4 substituents, - O-heteroaryl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-alkyl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-alkenyl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-alkynyl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-heteroaryl optionally substituted with 1, 2, 3, or 4 substituents, -NR6-aryl optionally substituted with 1, 2, 3, or 4 substituents, -NR8-C(O)R10, -NR8-S(O)- R3optionally substituted with 1, 2, 3, or 4 substituents, -NR8-C(S)-R3optionally substituted with 1, 2, 3, or 4 substituents, -NR8-S(O)(NR6)-R3optionally substituted with 1, 2, 3, or 4 substituents, -N=S(O)(R3)2optionally substituted with 1, 2, 3, or 4 substituents, -NR8C(O)NR9S(O)2R3optionally substituted with 1, 2, 3, or 4 substituents, -NR8-S(O)2-R10optionally substituted with 1, 2, 3, or 4 substituents, -NR8-C(NR6)- R3optionally substituted with 1, 2, 3, or 4 substituents, alkyl-C(O)-R3, -C(O)-R3, haloalkyl, -OC(O)R3,R1and R2may also form a 5 to 7 membered saturated heterocycle that comprises up to 3 heteroatoms selected from the group consisting of N, S and O and preferably the heterocycle is a 5 or 6- membered heterocycle;R1and R2may also form a 3 to 7 membered saturated optionally substituted carbocycle; the C4and C5atoms of Formula AG-1 to Formula AG-12 may be connected to form a 5 to 7 membered saturated optionally substituted heterocycle that comprises up to 3 heteroatoms selected from the group consisting of N, S and O; R3at each occurrence is independently selected from hydrogen, alkyl, heteroalkyl, haloalkyl (including -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CH2F, and -CF2CF3), arylalkyl, heteroarylalkyl, alkenyl, alkynyl, and, heteroaryl, heterocycle, -OR8, and -NR8R9; R4is independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR6, -NR6R7, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R5is independently selected from hydrogen, heteroalkyl,, C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, Cl, Br, I, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, -O-alkenyl, -O-alkynyl, C0-C6alkyl- OR6, C0-C6alkyl-SR6, C0- C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl- C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)- C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl- N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0- C6alkyl-O-S(O)R3, C0- C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, and C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, 3, or 4 substituents.R6and R7are independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, arylalkyl, heteroaryl alkyl, alkenyl, alkynyl, and, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R6and R7are independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, arylalkyl, heteroaryl alkyl, alkenyl, alkynyl, and, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3. R8and R9are independently selected at each occurrence from hydrogen, heteroalkyl, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocycle. R10is preferably selected from C5or C6heterocycles, bicyclic heterocycles, spirocyclic heterocycle, - NR6-heterocycle and more preferably from C5or C6heterocycles comprising 1 to 3 heteroatoms selected from N, O and S as ring atoms.R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, azide, amino, cyano, -NR6R7, -NR8SO2R3, -NR8S(O)R3, haloalkyl, heteroalkyl, and, heteroaryl, and heterocycle; R200is selected from , ,.

29. The compound of claim 25, wherein AG is a monosaccharide, disaccharide, or oligosaccharide, wherein one or more of the hydroxy (OH) groups in the particular sugar is be replaced with a -NRG2RG3group, wherein RG2and RG3are each independently selected from the group consisting of hydrogen and -C(=O)R and an optionally substituted C5 or C6 aromatic heterocycle, wherein R is C1-10alkyl, which is optionally substituted by 1-5 groups selected from the group consisting of halogen, C1-10alkoxy, C1-10aminoalkyl, and combinations thereof, or RG2and RG3taken together with the nitrogen atom to which they are attached, form a C5 heterocycle that is optionally substituted by 1-5 substituents selected from the group consisting of optionally substituted C1-10alkyl, optionally substituted C1-10alkoxy, optionally substituted C1-10aminoalkyl, optionally substituted C6-10aryl, optionally substituted C5-10heteroaryl, halogen, and combinations thereof.

30. The compound of any of the preceding claims, wherein AG has the structure,wherein T is selected from the group consisting of a direct bond and O and wherein * marks the bond that bounds AG to the remainder of the compound, with the proviso that no oxygen-oxygen bond is formed between AG and the remainder of the compounds of the present invention.

31. The compound of any of claims 29 or 30, wherein T is O, RG2is hydrogen and RG3is -C(=O)CH3.

32. The compound of any of claims 29 or 30, wherein RG2is hydrogen and RG3is an aromatic heterocycle selected from the group consisting of 1H-pyrrole, pyrazole, imidazole, furan, thiophene, oxazole, isoxazole, isothiazole, thiazole, triazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine.

33. The compound of any of claims 1 to 24, wherein AG is selected from the group consisting ofAG-(xi) AG-(xii) AG-(xiii) wherein the wavy lines mark the bond by which the sugar moiety is bonded to the remainder of the compounds of the present invention.

34. The compound of claim 33, wherein AG is selected from the group consisting of AG-(i) to AG(vii).

35. The compound of any of claims 33 or 34, wherein AG is selected from the group consisting of AG-(i), AG-(v) and AG-(vii).

36. The compound of any of the preceding claims, wherein Con is selected from the group consisting of alkyl, heteroalkyl,alkenyl, haloalkyl, carbocycle, aryl, heterocycle, and heteroaryl, each of which has three or four valences bonded to L1, L2, A and / or AG, respectively, and is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; wherein X- is a pharmaceutically acceptable anionic group, for example Br- or Cl-; J is a direct bond or a hydrocarbon with 1 to 10 carbon atoms and R6, R7 and R21 are as defined as in Claim 24.

37. The compound of any of the preceding claims, wherein Con is a hydrocarbon with 1 to 10 carbon atoms or a heterocycle with 5 to 8 ring members, wherein the hydrocarbon may be saturated or unsaturated and in which the heterocycle may be saturated or unsaturated, aromatic or aliphatic and comprise up to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and wherein in the hydrocarbon or the heterocycle one hydrogen atom is substituted by linker L1and n hydrogen atoms are substituted by linker L2.

38. The compound of Formula (II) of any of the preceding claims, wherein Con is -CH(3-n)(CH2-)n, wherein n is 2 or 3.

39. The compound of Formula (II) of any of the preceding claims, wherein one terminal end of L1is a –NH- residue, by which L1is bonded to Con and one terminal end of each of the n L2linkers are –O- residues, by which the linker L2are bonded to Con.

40. The compound of claims 1, 4, 23, 34 and 38 of Formula (I).

41. The compound of claims 1, 5, 23, 34 and 38 of Formula (I).

42. The compound of claims 1, 8, 23, 34 and 38 of Formula (I).

43. The compound of claims 1, 11, 23, 34 and 38 of Formula (I).

44. The compound of claims 1, 4, 23, 24, 34 and 38 of Formula (II).

45. The compound of claims 1, 5, 23, 24, 34 and 38 of Formula (II).

46. The compound of claims 1, 8, 23, 24, 34 and 38 of Formula (II).

47. The compound of claims 1, 11, 23, 24, 34 and 38 of Formula (II).

48. A method of preventing, treating, and / or ameliorating IgA nephropathy in a subject, the method comprising administering to the subject a composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of any of claims 1-47.

49. The method of claim 48 wherein the IgA Nephropathy is aggressive IgA Nephropathy.

50. The method of claim 48, wherein the IgA Nephropathy is familial IgA Nephropathy.

51. The method of any of claims 48 to 50, wherein the composition is administered by a route selected from the group consisting of oral, transdermal, transmucosal, (intra)nasal, (trans)rectal, intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical.

52. The method of any of claims 48 to 51, wherein the composition is administered intravenously.

53. The method of any of claims 48 to 52, wherein the composition is administered in a dose of 0.01 mg / kg to 20 mg / kg.

54. The method of any of claims 48 to 53, wherein the subject is a mammal.

55. The method of any of claims 48 to 54, wherein the subject is human.

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