Novel Peptides as Selective IL-23 Receptor Antagonists

Abstract

The present disclosure relates to, for example, peptide IL23 receptor antagonists, pharmaceutical compositions thereof and their medical use in the treatment of inflammatory bowel diseases such as Crohn's disease.

Description

Technical Field

[0001] The present disclosure relates to peptide IL-23 receptor antagonists and their medical use in the treatment of inflammatory bowel diseases such as Crohn's disease. The compounds disclosed herein are macrocyclic lactam peptides and exhibit high solubility and stability under neutral conditions and also in simulated intestinal and gastric fluids. The macrocyclic lactam peptides show high in vitro potency against the interleukin 23 receptor (IL-23R) with favorable physicochemical properties.

Background Art

[0002] Evidence is increasing that the interleukin-23 (IL-23) cytokine plays an important role in the etiology of autoimmune inflammation and related diseases and disorders such as asthma, rheumatoid arthritis, psoriasis, multiple sclerosis and inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease. The major role of IL-23R can be revealed by acute and chronic mouse models of IBD and the downstream effector cytokines in the etiology of the disease. Th17 cells, γδT cells, natural killer (NK) cells, dendritic cells, macrophages and innate lymphoid cells, which are abundant in the intestine, are adaptive and innate immune cells that express IL-23R. Patients with IBD have increased gene expression and IL-23R levels on the intestinal mucosal surface. There is evidence that IL-23 contributes to this effect by promoting the generation of pathogenic CD4+ T cell populations that produce IL-6, IL-17 and tumor necrosis factor (TNF).

[0003] The concentration of IL-23 increases in the intestine and is thought to play an important role in regulating the balance between tolerance and immunity via T cell-dependent and T cell-independent pathways of intestinal inflammation. This regulation affects T helper 1 (Th1) and Th17-related cytokines, suppresses regulatory T cell responses in the intestine, and promotes inflammation. Furthermore, IL-23R polymorphisms are associated with susceptibility to intestinal inflammation, further supporting the importance of the IL-23 pathway in intestinal homeostasis.

[0004] Psoriasis is a chronic skin disease with a prevalence of about 2% - 3% in the Caucasian population and is known to be mediated by the body's T-cell inflammatory response mechanism. Through the induction of interleukin-17, activation of macrophages, and regulation of T memory cells, IL-23 is one of several interleukins involved as a key player in the pathogenesis of psoriasis by maintaining chronic autoimmune inflammation. Neutralizing antibodies against IL-23 have shown IL-23-dependent inhibition of psoriasis development in animal models of psoriasis, but it has been demonstrated that the high expression of IL-23 and IL-23R increases in the tissues of psoriasis patients.

[0005] IL-23 is part of the IL-12 family of cytokines and is composed of a p19 subunit specific to IL-23 and the p40 subunit of IL-12, and is a cytokine involved in the development of interferon-y (IFN-y)-producing T helper 1 (TH1) cells. Both IL-23 and IL-12 contain the p40 subunit, but they have different phenotypic characteristics. Animals deficient in IL-12 are prone to inflammatory autoimmune diseases, while IL-23-deficient animals are resistant, probably because the number of CD4+ T cells producing IL-6, IL-17, and TNF in the CNS is reduced. IL-23 binds to IL-23R, a heterodimeric receptor composed of the IL-12Rβ1 and IL-23R subunits. When IL-23 binds to IL-23R, the Jak-Stat signaling molecules, Jak2, Tyk2, Stat1, Stat3, Stat4, and Stat5 are activated, but the activation of Stat4 is quite weak and forms different DNA-binding Stat complexes in response to IL-23 compared to IL-12. IL-23R constitutively associates with Jak2 and ligand-dependently associates with Stat3. In contrast to IL-12, which acts mainly on naive CD4(+) T cells, IL-23 preferentially acts on memory CD4(+) T cells.

[0006] Based on the importance of biology, inhibition of the IL-23 pathway is an attractive option for the treatment of IL-23 related diseases and disorders. Several antibodies that bind to IL-23 or IL-23R have been identified, such as ustekinumab, a humanized antibody that binds to IL-23 and is approved for the treatment of psoriasis. More recently, polypeptide inhibitors that bind to IL-23R and inhibit the binding of IL-23 to IL-23R have been identified (see, for example, US Patent Application Publication No. 2013 / 0029907). Clinical trials in Crohn's disease or psoriasis using ustekinumab and briakinumab (targeting the common p40 subunit) and tildrakizumab, guselkumab, brazikumab, and risankizumab (targeting the unique p19 subunit of IL-23) have highlighted the potential of IL-23 signaling blockade in the treatment of human inflammatory diseases. Although these findings are promising, there remains a challenge in identifying stable and selective agents that preferentially target the intestinal IL-23 pathway and can be used for the treatment of intestinal inflammation, such as intestinal diseases like Crohn's disease, ulcerative colitis, and related disorders.

[0007] Patients with inflammatory bowel disease (IBD) having autoimmune inflammation in the intestinal tract can benefit from oral-to-topical treatment where the compound specifically targets the IL-23 pathway from the luminal side of the intestine. The present disclosure addresses these needs by providing novel peptide compounds that bind to IL-23R and inhibit the binding and signaling of IL-23 and are suitable for oral administration. SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION

[0008] Problems associated with the use of peptide compounds as therapeutic agents for oral administration in the treatment of inflammatory diseases and other indications are limited stability in the intestinal environment. Thus, the peptide sequence can be stabilized by the introduction of non-genetically encoded amino acids and / or cyclized to enhance stability against proteases and enable interaction with targets located on the luminal side of the intestine.

[0009] Thus, in the development of new therapeutic molecules, variants are needed that have improved pharmaceutical properties, in particular increased stability against proteases present in the intestine and / or increased chemical or physical stability and / or an extended half-life in vivo and / or increased in vivo efficacy / effectiveness.

[0010] There is still a need for anti-inflammatory therapies that avoid or reduce the common systemic side effects of IL-23R-based therapies (e.g., defense against infection), thereby achieving a potent anti-inflammatory effect with improved tolerability.

[0011] Protagonist's International Publication Nos. WO2016011208A1, WO2017011820A2, WO2018022937A1, WO2018136646A1, WO2020014646, WO2021007433, WO2021146454, WO2021146458 and WO2021146441, and Sayago et al, ACS Med.Chem.Lett.2018, 9, 912 - 916 disclose peptide antagonists of the IL-23 receptor for oral administration. International Publication No. WO2022109328 discloses a composition of a cyclic peptide having the sequence Ac-Pen-Asn-Thr-Wim-Lys(Ac)-Pen-Yae-Nal-Thp-Glu-Asn-Pal-Sar-NH2, with a disulfide bond formed between the Pen residues. A common structural feature of the disclosed compounds is a ring formed by six amino acids as ring members.

[0012] International Publication No. WO2013063468 discloses cyclic peptides modified with long-chain hydrocarbon groups that result in amphiphilic molecules useful as drug delivery systems such as nucleotide delivery to cells.

[0013] International Publication No. 2015 / 179438 pamphlet also discloses a 2- to 10-membered cyclic peptide formed by amino acids as an inhibitor Rac or Rho in cells or tissues, wherein at least two amino acids are arginine.

[0014] The compounds of this disclosure exhibit high affinity for the IL-23 receptor.

[0015] The characteristic structural motif of the disclosed compounds includes a macrocyclic lactam ring having 34 to 40 atoms formed by 9, 10 or 11 amino acids as components, and a thioether, disulfide or ester bridge between the side chains of amino acids forming a second bicyclic structure having 5 or 6 amino acids as components.

[0016] Therefore, novel bicyclic peptides having high affinity for the IL-23 receptor are provided. Furthermore, the medical uses of these bicyclic peptides are provided.

Means for Solving the Problems

[0017] In this specification, formula (I):

Chemical formula

[0018] The compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0019] In a further aspect of any of the peptides described herein, the compound may comprise one or more half-life extending moieties and / or one or more linker moieties attached to the peptide.

[0020] In a further aspect, the compounds of the present disclosure can be compounds of formula (I) as described in further detail below.

[0021] In a further aspect, there is disclosed a composition comprising a compound of formula (I) or (Ia) as described herein, or a salt or solvate thereof, mixed with a carrier.

[0022] The present disclosure also relates to the use of a compound of formula (I) or formula (Ia) as described herein for use as a medicament, for example, for treating a condition as described herein.

[0023] The present disclosure also relates to a composition which is a pharmaceutically acceptable composition and wherein the carrier is a pharmaceutically acceptable carrier.

[0024] The present disclosure also relates to a pharmaceutical composition comprising a compound of formula (I) or formula (Ia) as described herein and at least a pharmaceutically acceptable carrier.

[0025] The present disclosure also relates to a pharmaceutical composition for use as a medicament, comprising at least one compound of the present disclosure, or a physiologically acceptable salt or solvate thereof, and at least a pharmaceutically acceptable carrier.

[0026] Definitions Amino acid. An amino acid is referred to herein by its name, by its generally known three-letter symbol, or by the one-letter symbol recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Thus, the amino acid sequences disclosed herein include the conventional one-letter and three-letter codes for naturally occurring amino acids, as well as the generally accepted three-letter codes for other amino acids, for example, Aib for α-aminoisobutyric acid, Orn for ornithine or Ahx for 6-aminohexanoic acid, and the like.

[0027] As used herein, the term "amino acid" or "any amino acid" refers to any amino acid, including naturally occurring amino acids (e.g., α-amino acids), non-natural amino acids, modified amino acids, and unnatural amino acids. It includes both D-amino acids and L-amino acids. Naturally occurring amino acids include those found in nature, such as the 22 amino acids that are incorporated into peptide chains to form the building blocks of a vast number of proteins. These are predominantly L-stereoisomers, although a small number of D-amino acids are present in bacterial envelopes and some antibiotics.

[0028] Unnatural or non-natural. "Unnatural" or "non-natural" amino acids are non-proteinogenic amino acids that do not occur naturally or are chemically synthesized (i.e., amino acids that are not naturally encoded or found in the genetic code). Over 140 unnatural amino acids are known, and thousands of further combinations are possible. Examples of "unnatural" amino acids include β-amino acids (β and β2), homoamino acids, proline and pyruvate derivatives, 3-substituted alanine derivatives, glycine derivatives, ring-substituted phenylalanine and tyrosine derivatives, linear core amino acids, diamino acids, D-amino acids, α-methyl amino acids, and N-methyl amino acids. Unnatural or non-natural amino acids also include modified amino acids. "Modified" amino acids include amino acids (e.g., natural amino acids) that have been chemically modified to contain one or more groups or chemical moieties that do not naturally occur on the amino acid.

[0029] Residue. Within the present disclosure, the term "residue" is intended to refer to a component within a peptide compound that results from the linkage of a natural amino acid, or a non-natural amino acid, or a compound such as Buty or Butyl.

[0030] "Inhibiting the binding of interleukin-23 to the interleukin-23 receptor". The expression "inhibiting the binding of interleukin-23 to the interleukin-23 receptor" is intended to refer to the property of the peptide compounds of the present disclosure that prevent the binding of the IL-23 receptor by its ligand IL-23. This property is measured as binding affinity and is the effective concentration of a compound that induces a decrease in the maximum half amount of the binding of IL-2.3 to its receptor in a dose-response experiment, which can be expressed as the "IC 50 value". The compounds of the present disclosure have a binding affinity for the interleukin-23 receptor of 100 nM or less (i.e., IC 50 ≤ 100 nM).

[0031] Furthermore, Table 1 shows the amino acids and the codes used for further compounds.

[0032]

Table 1

[0033]

Table 2

[0034]

Table 3

[0035]

Table 4

[0036]

Table 5

[0037]

Table 6

[0038]

Table 7

[0039]

Table 8

[0040]

Table 9

[0041]

Table 10

[0042]

Table 11

[0043]

Table 12

[0044]

Table 13

MODE FOR CARRYING OUT THE INVENTION

[0045] Peptide compound Compound of formula (I) In the present specification, formula (I):

Chemical formula

[0046] The compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0047] In some embodiments, the compound of formula (I) has X2 being an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and their corresponding d-forms, and X8 being an amino acid residue selected from the amino acid residues of Yme, Tyr, Trp and Yde, or Or an amino acid residue of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and an amino acid residue selected from the corresponding d-forms thereof, wherein X8 can be any one of amino acid residues selected from amino acid residues of Yme, Tyr, TrP, Yde and Yae.

[0048] In some embodiments, the compound of formula (I) may not have X8 as an amino acid residue of Yae when X2 is Abu or its corresponding d-form.

[0049] In some embodiments, the compound of formula (I) may not have X2 as an amino acid residue of Abu or its corresponding d-form when X8 is Yae.

[0050] In the first group of embodiments, the compound of formula (I) - X1 is a residue of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad or Dap, and is bonded to X11 via an amide bond, or X1 is a residue of Buty or Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond. - R1 is absent or When X1 is a residue of Ahx, Aoa, Apt, Lys, Dab or Dap, R1 is H, C1-C4-alkyl or acetyl, and is bonded to the amino functional group of X1. - X2 is an amino acid residue of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr or Abu, and their corresponding d-forms. - X7 is an amino acid residue of Cys, Glu, Asp, Thr or Abu, and their corresponding d-forms. X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond. -X3 is an amino acid residue of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk or Lys(αAc), -X4 is absent or is an amino acid residue of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp or Thr, -X5 is an amino acid residue of Trp, Wme, Nak, Wcl, Wim, Wdm or Wfl, -X6 is an amino acid residue of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp or Phe, -X8 is an amino acid residue of Yme, Tyr, Trp or Yde, -X9 is an amino acid residue of Nal, Nak or Trp, -X10 is an amino acid residue of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm or Thp, -X11 is an amino acid residue of Asp, Bal, Gab, Glu, Kme, Lys or Orn, and is bonded to X1 via an amide bond, -X12 is absent or is an amino acid residue of Asn, Gly, Ser or Ala, -X13 is absent or is an amino acid residue of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme or Val, and their corresponding d-forms, -X14 is absent or is an amino acid residue of Mep, Sar, Bal, Ile, Dnmy or Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH or -N(C2H5)2, The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, between X11 and X1 are optionally methylated, or may be a salt or solvate thereof.

[0051] In such a group of embodiments, the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0052] In some embodiments of the first group of embodiments, the compound of formula (I) - X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, and is bonded to X11 via an amide bond, or X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, - R1 is absent or when X1 is a residue selected from the residues of Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl, and is bonded to the amino functional group of X1, - X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, - X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, - X3 is an amino acid residue selected from the residues of Apt, Asn, Ndmk, Nmn and Lys(αAc), - X4 is absent or is an amino acid residue of Thr, - X5 is an amino acid residue selected from the residues of Trp, Wme and Wim, - X6 is an amino acid residue selected from the residues of Gln, Lys(Ac) and Leu, - X8 is an amino acid residue selected from the residues of Yme, Trp and Yde, - X9 is an amino acid residue of Nal, -X10 is an amino acid residue selected from residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm, and Thp, -X11 is an amino acid residue selected from residues of Asp, Glu, Kme, Lys, and Orn, and is bonded to X1 via an amide bond, -X12 is absent or is an amino acid residue selected from residues of Asn, Gly, Ser, and Ala, -X13 is absent or is an amino acid residue selected from residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His, and Hme, -X14 is absent or is an amino acid residue selected from residues of Mep, Sar, Bal, Ile, and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH, or -N(C2H5)2, or may be a salt or solvate thereof.

[0053] In a second group of embodiments, the compound of formula (I) is -X1 is a residue selected from residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad, and Dap, and is bonded to X11 via an amide bond, or X1 is a residue selected from residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is absent or when X1 is a residue selected from residues of Ahx, Aoa, Apt, Lys, Dab, and Dap, R1 is H, C1-C4-alkyl, or acetyl and is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and their corresponding d-forms, -X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is a disulfide bond, a thioether bond or an ester bond, -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), -X4 is either absent or an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde and Yae, -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is linked to X1 via an amide bond, -X12 is either absent or an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, -X13 is absent or is an amino acid residue selected from residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, Val, and the corresponding d-forms thereof, -X14 is absent or is an amino acid residue selected from residues of Mep, Sar, Bal, Ile, Dnmy and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH or -N(C2H5)2, The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, between X11 and X1 are optionally methylated, or a salt or solvate thereof.

[0054] In such a group of embodiments, the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0055] In some embodiments of a second group of embodiments, the compound of formula (I) -X1 is a residue selected from residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, which is bonded to X11 via an amide bond, or X1 is a residue selected from residues of Buty and Butyl, which is bonded to X11 via an alkyl bond, and when X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is absent or when X1 is a residue selected from residues of Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl, which is bonded to the amino function of X1, -X2 is an amino acid residue selected from residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, and Thr, -X7 is an amino acid residue selected from residues of Cys, Glu, Asp, Thr and Abu, X2 and X7 are coupled to each other via Q, where Q is a disulfide bond, a thioether bond or an ester bond, -X3 is an amino acid residue selected from the residues of Apt, Asn, Ndmk, Nmn and Lys(αAc), -X4 is absent or is an amino acid residue of Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme and Wim, -X6 is an amino acid residue selected from the residues of Gln, Lys(Ac) and Leu, -X8 is an amino acid residue selected from the residues of Yme, Trp, Yde and Yae, -X9 is an amino acid residue of Nal, -X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Glu, Kme, Lys and Orn, and is coupled to X1 via an amide bond, -X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, -X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His and Hme, -X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile and Hme, -X15 is absent or is the amino acid residue Lys, -R2 is absent or is -NH2, -OH or -N(C2H5)2, or may be a salt or solvate thereof.

[0056] An embodiment of the compound of formula (I) is an embodiment in which R1 is absent.

[0057] An embodiment of the compound of formula (I) is an embodiment in which R1 is H.

[0058] An embodiment of the compound of formula (I) is an embodiment in which R1 is C1-C4-alkyl.

[0059] An embodiment of the compound of formula (I) is an embodiment in which R1 is acetyl.

[0060] An embodiment of the compound of formula (I) is an embodiment in which R2 is absent.

[0061] An embodiment of the compound of formula (I) is an embodiment in which R2 is -NH2.

[0062] An embodiment of the compound of formula (I) is an embodiment in which R2 is -OH.

[0063] An embodiment of the compound of formula (I) is an embodiment in which R2 is -N(C2H5)2.

[0064] One embodiment of the compound of formula (I) is

[0065] X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab and Dap, and X11 is an amino acid residue selected from the residues of Asp and Glu, or or, X1 is a residue of Dad, and X11 is an amino acid residue selected from the residues of Lys and Kme, or or, X1 is a residue selected from the residues of Buty and Butyl, and X11 is an amino acid residue of Kme, which is an embodiment.

[0066] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Ahx and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0067] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Apt and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0068] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Apt and X11 is an amino acid residue of Glu.

[0069] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Nmapt and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0070] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Nmapt and X11 is an amino acid residue of Glu.

[0071] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Nmapt and X11 is an amino acid residue of Asp.

[0072] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Nmha and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0073] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Nmha and X11 is an amino acid residue of Glu.

[0074] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Nmha and X11 is an amino acid residue of Asp.

[0075] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Lys and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0076] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Lys and X11 is an amino acid residue of Glu.

[0077] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Lys and X11 is an amino acid residue of Asp.

[0078] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Dad and X11 is an amino acid residue selected from the residues of Lys or Kme.

[0079] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Dad and X11 is an amino acid residue of Lys.

[0080] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Dad and X11 is an amino acid residue of Kme.

[0081] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Buty and X11 is an amino acid residue selected from the residues of Lys or Kme.

[0082] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Buty and X11 is an amino acid residue of Lys.

[0083] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Buty and X11 is an amino acid residue of Kme.

[0084] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Butyl and X11 is an amino acid residue selected from the residues of Lys or Kme.

[0085] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Butyl and X11 is an amino acid residue of Lys.

[0086] An embodiment of the compound of formula (I) is an embodiment in which X1 is a residue of Butyl and X11 is an amino acid residue of Kme.

[0087] In some embodiments of the first group of embodiments, X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr, and Abu, and their corresponding d-forms.

[0088] In some embodiments of the second group of embodiments, X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, and Thr, and their corresponding d-forms.

[0089] In an embodiment of the compound of formula (I), X2 is an amino acid residue selected from the residues of Cys and Nmc, and their corresponding d-forms, X7 is an amino acid residue selected from the residue of Cys and its corresponding d-form, X2 and X7 are linked to each other via Q, where Q is a disulfide bond, or, X2 is an amino acid residue selected from the residues of Cys, Nmc, Thr, and Abu, and their corresponding d-forms, X7 is an amino acid residue selected from the residues of Cys, Thr, and Abu, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is a thioether bond, or, X2 is an amino acid residue selected from the residues of Glu, Asp, Nmd, Nme, Nmt, and Thr, and their corresponding d-forms, X7 is an amino acid residue selected from the residues of Glu, Asp, Thr, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is an ester bond, which is an embodiment.

[0090] In an embodiment of the compound of formula (I), X2 is an amino acid residue selected from the residue of Cys and its corresponding d-form, X7 is an amino acid residue selected from the residue of Cys and its corresponding d-form, X2 and X7 are linked to each other via Q, where Q is a disulfide bond, or or, X2 is an amino acid residue selected from the residues of Cys, Glu, Thr, and Abu, and their corresponding d-forms, X7 is an amino acid residue selected from the residues of Cys, Thr, and Abu, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is a thioether bond, or or, X2 is an amino acid residue selected from the residues of Glu and Thr, and their corresponding d-forms, X7 is an amino acid residue selected from the residues of Glu, Asp, and Thr, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is an ester bond, which is an embodiment.

[0091] In an embodiment of the compound of formula (I), X2-Q-X7 is Cys-Q-Cys, Nmc-Q-Cys, and Cys-Q-Nmc (Q is a disulfide bond), or Abu-Q-Cys, Cys-Q-Abu (Q is a thioether bond), or Thr-Q-Asp, Thr-Q-Glu, Glu-Q-Thr (Q is an ester bond), which is an embodiment selected from the group.

[0092] In some embodiments of the first group of embodiments, the compound of formula (I) has X2-Q-X7 being -Cys-Q-Cys, Nmc-Q-Cys, and Cys-Q-Nmc (Q is a disulfide bond), or -Abu-Q-Cys, Cys-Q-Abu (Q is a thioether bond), or -Thr-Q-Asp, Thr-Q-Glu, Glu-Q-Thr (Q is an ester bond), which is a compound selected from the group.

[0093] In some embodiments of the second group of embodiments, for the compound of formula (I), X2-Q-X7 is -Cys-Q-Cys, Nmc-Q-Cys and Cys-Q-Nmc (Q is a disulfide bond), or -Cys-Q-Abu (Q is a thioether bond), or -Thr-Q-Asp, Thr-Q-Glu, Glu-Q-Thr (Q is an ester bond), and is a compound selected from the group consisting of.

[0094] An embodiment of the compound of formula (I) is an embodiment in which X2-Q-X7 is selected from the group consisting of Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond), or Abu-Q-Cys (Q is a thioether bond), or Glu-Q-Thr (Q is an ester bond).

[0095] An embodiment of the compound of formula (I) is an embodiment in which X2-Q-X7 is selected from the group consisting of Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond).

[0096] An embodiment of the compound of formula (I) is an embodiment in which X2-Q-X7 is Abu-Q-Cys (Q is a thioether bond).

[0097] An embodiment of the compound of formula (I) is an embodiment in which X2-Q-X7 is Glu-Q-Thr (Q is an ester bond).

[0098] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue selected from the residues of Apt, Ndmk, Nmn and Lys(αAc).

[0099] An embodiment of the compound of formula (I) is an embodiment in which X3 is the amino acid residue of Sar.

[0100] An embodiment of the compound of formula (I) is an embodiment in which X3 is the amino acid residue of His.

[0101] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Lys.

[0102] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Ala.

[0103] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Ahx.

[0104] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Apt.

[0105] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Arg.

[0106] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Asn.

[0107] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Gab.

[0108] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Gln.

[0109] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Trp.

[0110] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Thr.

[0111] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Ndmk.

[0112] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Nmn.

[0113] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Ntmk.

[0114] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Lys(αAc).

[0115] An embodiment of the compound of formula (I) is an embodiment in which X4 is absent.

[0116] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue selected from the residues of Lys, Ahx, Apt, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), and X4 is absent.

[0117] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue selected from the residues of Apt, Ndmk, Nmn and Lys(αAc), and X4 is absent.

[0118] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue selected from the residues of Apt, Ndmk and Lys(αAc), and X4 is absent.

[0119] An embodiment of the compound of formula (I) is an embodiment in which X3 is an amino acid residue of Lys(αAc), and X4 is absent.

[0120] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue selected from the residues of His, Lys, Arg, Asn, Gab, Gln, Trp and Thr.

[0121] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue selected from the residues of His, Lys, Arg, Asn, Gln, Trp and Thr.

[0122] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of His.

[0123] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Lys.

[0124] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Ahx.

[0125] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Apt.

[0126] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Arg.

[0127] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Asn.

[0128] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Gab.

[0129] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Gln.

[0130] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Trp.

[0131] An embodiment of the compound of formula (I) is an embodiment in which X4 is an amino acid residue of Thr.

[0132] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl.

[0133] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue selected from the residues of Trp, Wme, Wcl, Wim, Wdm and Wfl.

[0134] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue selected from Trp and Wim.

[0135] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue of Trp.

[0136] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue of Wme.

[0137] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue of Nak.

[0138] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue of Wcl.

[0139] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue of Wim.

[0140] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue of Wdm.

[0141] An embodiment of the compound of formula (I) is an embodiment in which X5 is an amino acid residue of Wfl.

[0142] An embodiment of the compound of formula (I) is an embodiment in which X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe.

[0143] An embodiment of the compound of formula (I) is an embodiment in which X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva and Val.

[0144] An embodiment of the compound of formula (I) is an embodiment in which X6 is an amino acid residue selected from the residues of Gln, Lys(Ac) and Leu.

[0145] An embodiment of the compound of formula (I) is an embodiment in which X6 is an amino acid residue of Gln.

[0146] An embodiment of the compound of formula (I) is an embodiment in which X6 is an amino acid residue of Aib.

[0147] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Glu.

[0148] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Phe.

[0149] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Ile.

[0150] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Iva.

[0151] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Lys.

[0152] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Lys(Ac).

[0153] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Leu.

[0154] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Mle.

[0155] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Mly.

[0156] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Mva.

[0157] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Thr.

[0158] An embodiment of the compound of formula (I) is an embodiment in which the amino acid residue of X6 is Val.

[0159] An embodiment of the compound of formula (I) is an embodiment in which X6 is an amino acid residue of Trp.

[0160] An embodiment of the compound of formula (I) is an embodiment in which X6 is an amino acid residue of Phe.

[0161] An embodiment of the compound of formula (I) is an embodiment in which X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde and Yae.

[0162] In some embodiments of the first group of embodiments, X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp and Yde.

[0163] In some embodiments of the second group of embodiments, X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde and Yae.

[0164] An embodiment of the compound of formula (I) is an embodiment in which X8 is an amino acid residue selected from the residues of Yme, Yde and Yae.

[0165] An embodiment of the compound of formula (I) is an embodiment in which X8 is an amino acid residue of Yme.

[0166] An embodiment of the compound of formula (I) is an embodiment in which X8 is an amino acid residue of Tyr.

[0167] An embodiment of the compound of formula (I) is an embodiment in which X8 is an amino acid residue of Trp.

[0168] An embodiment of the compound of formula (I) is an embodiment in which X8 is an amino acid residue of Yde.

[0169] An embodiment of the compound of formula (I) is an embodiment in which X8 is an amino acid residue of Yae.

[0170] An embodiment of the compound of formula (I) is an embodiment in which X9 is an amino acid residue of Nal.

[0171] An embodiment of the compound of formula (I) is an embodiment in which X9 is the amino acid Nak.

[0172] An embodiment of the compound of formula (I) is an embodiment in which X9 is the amino acid residue of Trp.

[0173] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp.

[0174] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm and Thp.

[0175] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue selected from the residues of Aib, Mle, Mly, Mkdm and Thp.

[0176] An embodiment of the compound of formula (I) is an embodiment in which X10 is the amino acid residue of Aib.

[0177] An embodiment of the compound of formula (I) is an embodiment in which X10 is the amino acid residue of Cba.

[0178] An embodiment of the compound of formula (I) is an embodiment in which X10 is the amino acid residue of Cit.

[0179] An embodiment of the compound of formula (I) is an embodiment in which X10 is the amino acid residue of d-Trp.

[0180] An embodiment of the compound of formula (I) is an embodiment in which X10 is the amino acid residue of d-Tza.

[0181] An embodiment of the compound of formula (I) is an embodiment in which X10 is the amino acid residue of Lys.

[0182] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue of Lys(Ac).

[0183] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue selected from Leu.

[0184] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue of Mle.

[0185] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue of Mly.

[0186] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue of Gln.

[0187] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue of Mkdm.

[0188] An embodiment of the compound of formula (I) is an embodiment in which X10 is an amino acid residue of Thp.

[0189] An embodiment of the compound of formula (I) is an embodiment in which X12 is absent or is an amino acid residue selected from the residues of Asn, Ser and Ala.

[0190] An embodiment of the compound of formula (I) is an embodiment in which X12 is absent.

[0191] An embodiment of the compound of formula (I) is an embodiment in which X12 is an amino acid residue of Asn.

[0192] An embodiment of the compound of formula (I) is an embodiment in which X12 is an amino acid residue of Ser.

[0193] An embodiment of the compound of formula (I) is an embodiment in which X12 is an amino acid residue of Ala.

[0194] Embodiments of the compound of formula (I) are embodiments in which X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, His, Mhis, Val and their corresponding d-forms.

[0195] Embodiments of the compound of formula (I) are embodiments in which X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, d-Leu, Ile, Iva, Hol, Hph, Pal, Pyal, His, Hme and Val.

[0196] Embodiments of the compound of formula (I) are embodiments in which X13 is absent or is an amino acid residue selected from the residues of Asn, Gly, d-Leu, Pal and His.

[0197] Embodiments of the compound of formula (I) are embodiments in which X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy and Hme.

[0198] Embodiments of the compound of formula (I) are embodiments in which X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal and Ile.

[0199] Embodiments of the compound of formula (I) are embodiments in which X14 is absent.

[0200] Embodiments of the compound of formula (I) are embodiments in which X14 is an amino acid residue selected from the residues of Mep, Sar, Bal and Ile.

[0201] Embodiments of the compound of formula (I) are embodiments in which X14 is the amino acid residue of Sar.

[0202] Embodiments of the compound of formula (I) are embodiments in which X15 is absent or is the amino acid residue of Lys.

[0203] An embodiment of the compound of formula (I) is an embodiment in which X15 is absent.

[0204] An embodiment of the compound of formula (I) is an embodiment in which X15 is an amino acid residue of Lys.

[0205] In a third group of embodiments, the compound of formula (I) is X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, and is bonded to X11 via an amide bond, or X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, either R1 is absent, or when X1 is a residue selected from the residues of Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl, X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, X3 is an amino acid residue selected from the residues of Apt, Asn, Ndmk, Nmn and Lys(αAc), either X4 is absent or X4 is an amino acid residue of Thr, X5 is an amino acid residue selected from the residues of Trp, Wme and Wim, X6 is an amino acid residue selected from the residues of Gln, Lys(Ac) and Leu, X8 is an amino acid residue selected from the residues of Yme, Trp, Yde and Yae, X9 is an amino acid residue of Nal, X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm, and Thp, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme, Lys, and Orn, and is bonded to X1 via an amide bond, X12 is either absent or is an amino acid residue selected from the residues of Asn, Gly, Ser, and Ala, X13 is either absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, PyAl, PyEA, His, and Hme, X14 is either absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, and Hme, X15 is either absent or is an amino acid residue of Lys, R2 is either absent or is -NH2, -OH, or -N(C2H5)2, a compound or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0206] In the third group of embodiments, for the compound of formula (I), X2 is an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr, and Abu, and X8 is an amino acid residue selected from the amino acid residues of Yme, Trp, and Yde, or an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, and Thr, and X8 is an amino acid residue selected from the amino acid residues of Yme, Trp, Yde, and Yae.

[0207] In the fourth group of embodiments, for the compound of formula (I), X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, and is bonded to X11 via an amide bond, or alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond, and when X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, R1 is absent or, when X1 is selected from the groups of Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl and is bonded to the amino functional group of X1, X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, X2 and X7 are bonded to each other via Q, where Q is a disulfide bond, a thioether bond or an ester bond, X3 is an amino acid residue selected from the residues of Asn and Nmn, X4 is the amino acid residue of Thr, X5 is an amino acid residue selected from the residues of Trp, Wme and Wim, X6 is Gln, X8 is an amino acid residue selected from the residues of Yme, Trp, Yde and Yae, X9 is the amino acid residue of Nal, X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm and Thp, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, X13 is either absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His and Hme, X14 is either absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile and Hme, X15 is either absent or is an amino acid residue of Lys, R2 is either absent or is -NH2, -OH or -N(C2H5)2, a compound, or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0208] In a fourth group of embodiments, for the compound of formula (I), X2 is an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and X8 is an amino acid residue selected from the amino acid residues of Yme, Trp and Yde, or or, an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and X8 is an amino acid residue selected from the amino acid residues of Yme, Trp, Yde and Yae, either one of which may be the case.

[0209] In a fifth group of embodiments, for the compound of formula (I), X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, and is bonded to X11 via an amide bond, or alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond, and when X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, R1 is absent, or when X1 is selected from the residues of Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl, and is bonded to the amino functional group of X1, X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, X3 is an amino acid residue selected from the residues of Apt, Ndmk and Lys(αAc), X4 is absent, X5 is an amino acid residue selected from the residues of Trp, Wme and Wim, X6 is Gln, X8 is an amino acid residue selected from the residues of Yme, Trp, Yde and Yae, X9 is the amino acid residue of Nal, X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm and Thp, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, X12 is absent, or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, X13 is absent, or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His and Hme, X14 is absent, or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile and Hme, X15 is absent, or is the amino acid residue of Lys, R2 is absent, or is -NH2, -OH or -N(C2H5)2, a compound, or a salt or solvate thereof, wherein the compound of formula (I) is a compound or a salt or solvate thereof that inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0210] In a fifth group of embodiments, for the compound of formula (I), X2 is an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and X8 is an amino acid residue selected from the amino acid residues of Yme, Trp and Yde, or an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr Abu, and X8 may be an amino acid residue selected from the amino acid residues of Yme, Trp, Yde and Yae.

[0211] In a sixth group of embodiments, for the compound of formula (I), R 1 is absent or is H, C1-C4-alkyl or acetyl, and is attached to the amino functionality of X1, X1 is a residue of Apt and is attached to X11 via an amide bond, X2 is an amino acid residue of Cys, X7 is an amino acid residue of Cys, X2 and X7 are attached to each other via Q, where Q is a disulfide bond, or X3 is an amino acid residue selected from the residues of Asn and Lys(αAc), X4 is absent or is an amino acid residue of Thr, X5 is an amino acid residue of Wim, X6 is an amino acid residue of Lys(Ac), X8 is an amino acid residue of Yde, X9 is an amino acid residue of Nal, X10 is an amino acid residue selected from the residues of Mkdm and Thp, X11 is an amino acid residue of Glu, which is bonded to X1 via an amide bond, X12 is an amino acid residue of Asn, X13 is an amino acid residue of Pal, X14 is an amino acid residue of Sar, X15 does not exist, R2 is -NH 2 A compound, or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0212] In the seventh group of embodiments, the compound of formula (I) R1 is absent or is H, C1-C4-alkyl or acetyl and is bonded to the amino function of X1, X1 is a residue of Apt and is bonded to X11 via an amide bond, X2 is an amino acid residue of Cys, X7 is an amino acid residue of Cys, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, X3 is an amino acid residue of Asn, X4 is an amino acid residue of Thr, X5 is an amino acid residue of Wim, X6 is an amino acid residue of Lys(Ac), X8 is an amino acid residue of Yde, X9 is an amino acid residue of Nal, X10 is an amino acid residue selected from the residues of Mkdm and Thp, X11 is an amino acid residue of Glu, which is bonded to X1 via an amide bond, X12 is an amino acid residue of Asn, X13 is an amino acid residue of Pal, X14 is an amino acid residue of Sar, X15 is absent, R2 is -NH 2 a compound, or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor, a compound or a salt or solvate thereof.

[0213] In the eighth group of embodiments, the compound of formula (I) is R1 is absent or is H, C1-C4-alkyl or acetyl, and is attached to one of the amino functional groups, X1 is a residue of Apt and is attached to X11 via an amide bond, X2 is an amino acid residue of Cys, X7 is an amino acid residue of Cys, X2 and X7 are attached to each other via Q, and Q is a disulfide bond, X3 is an amino acid residue of Lys(αAc), X4 is absent, X5 is an amino acid residue of Wim, X6 is an amino acid residue of Lys(Ac), X8 is an amino acid residue of Yde, X9 is an amino acid residue of Nal, X10 is an amino acid residue selected from the residues of Mkdm and Thp, X11 is an amino acid residue of Glu and is attached to X1 via an amide bond, X12 is an amino acid residue of Asn, X13 is an amino acid residue of Pal, X14 is an amino acid residue of Sar, X15 is absent, R2 is -NH 2 a compound, or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor, a compound or a salt or solvate thereof.

[0214] In the ninth group of embodiments, the compound of formula (I) is R1 is absent or, when X1 is selected from Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl, and is attached to the amino function of X1, X1 is a residue selected from residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad and is attached to X11 via an amide bond, or or X1 is a residue selected from residues of Buty and Butyl and is attached to X11 via an alkyl bond, and when X1 is a residue of Butyl, the residue of Butyl is attached to X2 via an alkyl bond, X2 is an amino acid residue selected from residues of Cys, Nmc and Abu, X7 is an amino acid residue selected from residues of Cys, Glu, Asp and Thr, X2 and X7 are attached to each other via Q, where Q is a disulfide bond, a thioether bond or an ester bond, X3 is the amino acid residue of Lys(αAc), X4 is absent, X5 is an amino acid residue selected from residues of Trp and Wim, X6 is the amino acid residue of Lys(Ac), X8 is the amino acid residue of Yde, X9 is the amino acid residue of Nal, X10 is an amino acid residue selected from residues of Mkdm and Thp, X11 is an amino acid residue selected from residues of Asp, Glu, Kme and Lys and is attached to X1 via an amide bond, X12 is the amino acid residue of Gly, X13 is the amino acid residue of PyEA, X14 is absent, X15 is absent, R2 is absent, a compound, or a salt or solvate thereof, provided that the compound of formula (I) is a compound or a salt or solvate thereof that inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0215] In a tenth group of embodiments, the compound of formula (I) is such that X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys, Dad, and is bonded to X11 via an amide bond, R1 is absent or, when X1 is selected from the residues of Ahx, Aoa, Apt, Lys, Dab, and Dap, R1 is H, C1-C4-alkyl or acetyl and is bonded to the amino function of X1, X2-Q-X7 is selected from Cys-Q-Cys and Nmc-Q-Cys (where Q is a disulfide bond), or Abu-Q-Cys (where Q is a thioether bond), or Glu-Q-Thr (where Q is an ester bond), X3 is the amino acid residue of Lys(αAc) and X4 is absent, or alternatively, X3 is the amino acid residue of Asn and X4 is the amino acid residue of Thr, X5 is an amino acid residue selected from the residues of Trp and Wim, X6 is an amino acid residue selected from the residues of Gln and Lys(Ac), X8 is an amino acid residue selected from the residues of Yme, Yde, and Yae, X9 is the amino acid residue of Nal, X10 is an amino acid residue selected from the residues of Aib, Mle, Mly, Mkdm, and Thp, X11 is an amino acid residue selected from the residues of the group consisting of Asp, Glu, Kme, and Lys, and is bonded to X1 via an amide bond, X12 is an amino acid residue selected from the residues of Asn, Ser, and Ala, X13 is an amino acid residue selected from the residues of Asn, Gly, d-Leu, Pal, and His, X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, and Ile, X15 is absent, R2 is -NH2, a compound, or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor, a compound or a salt or solvate thereof.

[0216] In some embodiments of the tenth group of embodiments, the compound of formula (I) is X2-Q-X7 is selected from Cys-Q-Cys and Nmc-Q-Cys (where Q is a disulfide bond), or Abu-Q-Cys (where Q is a thioether bond), or Glu-Q-Thr (where Q is an ester bond), and X8 is an amino acid residue selected from the residues of Yme and Yde, or X7 is selected from Cys-Q-Cys and Nmc-Q-Cys (where Q is a disulfide bond) or Glu-Q-Thr (where Q is an ester bond), and X8 is an amino acid residue selected from the residues of Yme, Yde, and Yae.

[0217] In the eleventh group of embodiments, for the compound of formula (I), X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Gln-Cys, Cys-Asn-Thr-Wim-Gln-Cys, Cys-Asn-Thr-Trp-Lys(Ac)-Cys, Cys-Asn-Thr-Wim-Lys(Ac)-Cys, Cys-Nmn-Thr-Trp-Gln-Cys, Abu-Asn-Thr-Trp-Lys(Ac)-Cys, Abu-Asn-Thr-Wim-Lys(Ac)-Cys and Abu-Asn-Thr-Wme-Leu-Cys.

[0218] In the twelfth group of embodiments, for the compound of formula (I), X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Lys(Ac)-Cys, Cys-Asn-Thr-Wim-Lys(Ac)-Cys, Cys-Nmn-Thr-Trp-Gln-Cys, Abu-Asn-Thr-Trp-Lys(Ac)-Cys and Abu-Asn-Thr-Wim-Lys(Ac)-Cys, and is a compound selected therefrom.

[0219] In the thirteenth group of embodiments, for the compound of formula (I), X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Lys(Ac)-Cys and Cys-Asn-Thr-Wim-Lys(Ac)-Cys, and is a compound selected therefrom.

[0220] In the fourteenth group of embodiments, for the compound of formula (I), X2-X3-X5-X6-X7 is Cys-Lys(αAc)-Trp-Gln-Cys, Cys-Lys(αAc)-Wim-Gln-Cys, Cys-Lys(αAc)-Trp-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Lys(Ac)-Cys, Cys-Ndmk-Trp-Lys(Ac)-Cys, Cys-Ndmk-Wim-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Leu-Cys, Nmc-Lys(αAc)-Wim-Leu-Cys, Cys-Apt-Trp-Gln-Cys, Abu-Lys(αAc)-Trp-Lys(Ac)-Cys, Abu-Lys(αAc)-Wim-Lys(Ac)-Cys, and Glu-Apt-Trp-Gln-Thr, and is selected from It is a compound in which X4 is absent.

[0221] In the 15th group of embodiments, for the compound of formula (I), X2-X3-X5-X6-X7 is Cys-Lys(αAc)-Trp-Gln-Cys, Cys-Lys(αAc)-Wim-Gln-Cys, Cys-Lys(αAc)-Trp-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Lys(Ac)-Cys, Cys-Ndmk-Trp-Lys(Ac)-Cys, Cys-Ndmk-Wim-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Leu-Cys, Nmc-Lys(αAc)-Wim-Leu-Cys and is selected from Cys-Apt-Trp-Gln-Cys, It is a compound in which X4 is absent.

[0222] In the 16th group of embodiments, for the compound of formula (I), X2-X3-X5-X6-X7 is Cys-Lys(αAc)-Trp-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Lys(Ac)-Cys, Cys-Ndmk-Trp-Lys(Ac)-Cys and is selected from Cys-Ndmk-Wim-Lys(Ac)-Cys, It is a compound in which X4 is absent.

[0223] In the 17th group of embodiments, for the compound of formula (I), X8-X9-X10 is X8-Nal-X10, where X8 is selected from the residues of Yae, Yde and Yme, and X10 is selected from the residues of Aib, Mle, Thp, Mkdm and Mly.

[0224] In the 18th group of embodiments, for the compound of formula (I), X8-X9-X10 is Yde-Nal-X10, and X10 is a residue selected from the residues of Aib, Mle, Thp, Mkdm and Mly.

[0225] In the 19th group of embodiments, for the compound of formula (I), X8-X9-X10 is Yde-Nal-Aib, Yde-Nal-Mle, Yde-Nal-Thp, Yde-Nal-Mkdm, Yde-Nal-Mly, Yme-Nal-Aib, Yae-Nal-Mle, Yae-Nal-Thp, Yme-Nal and a compound selected from Yde-Nal-Aib.

[0226] In the 20th group of embodiments, for the compound of formula (I), X12-X13- is a compound selected from Asn-Asn-, Asn-Gly-, Asn-d-Leu-, Ala-Gly-, Ala-d-Leu-, Asn-His-, Ser-His-, Asn-Pal-, Asn-Pyal- and Gly-PyEA-.

[0227] In the 21st group of embodiments, for the compound of formula (I), X12-X13- is Gly-PyEA, X14 does not exist, X15 does not exist, and R2 does not exist.

[0228] In the 22nd group of embodiments, for the compound of formula (I), X12-X13- is selected from Asn-Asn-, Asn-Gly-, Asn-d-Leu-, Ala-Gly-, Ala-d-Leu-, Asn-His-, Ser-His-, Asn-Pal- and Asn-Pyal-, X14 does not exist, X15 does not exist, and R2 is NH2 and does not exist.

[0229] In the twenty-third group of embodiments, the compound of formula (I) is a compound in which X12-X13-X14- is selected from Asn-Pal-Sar-, Asn-Pal-Ile-, Asn-Asn-Ile-, Asn-His-Sar, Asn-His-Bal-, Asn-His-Mep-, Ser-Pal-Sar- and Ala-Pal-Sar-.

[0230] In the twenty-fourth group of embodiments, the compound of formula (I) is a compound in which X12-X13-X14- is selected from Asn-Pal-Sar-, Asn-Pal-Ile-, Asn-Asn-Ile-, Asn-His-Sar, Asn-His-Bal-, Asn-His-Mep-, Ser-Pal-Sar-, Ala-Pal-Sar-, Asn-Asn-absent-, Asn-Gly-absent-, Asn-d-Leu-absent-, Ala-Gly-absent-, Ala-d-Leu-absent-, Asn-His-absent-, Ser-His-absent-, Asn-Pal-absent-, Asn-Pal-absent-, Asn-absent-absent-, Asn-Pyal-absent- and Gly-PyEA-absent-.

[0231] In the twenty-fifth group of embodiments, the compound of formula (I) is a compound in which X12-X13-X14-X15 is selected from the group consisting of Asn-Asn-absent-absent-, Asn-Gly-absent-absent-, Asn-d-Leu-absent-absent-, Ala-Gly-absent-absent-, Ala-d-Leu-absent-absent-, Asn-His-absent-absent-, Ser-His-absent-absent-, Asn-Pal-absent-absent-, Asn-Pal-Sar-absent-, Asn-Pal-Sar-Lys, Asn-Pal-Ile-absent-, Asn-Asn-Ile-absent-, Asn-His-Sar-absent-, Asn-His-Bal-absent-, Asn-His-Mep-absent, Ser-Pal-Sar-absent-, Ala-Pal-Sar-absent-, Asn-Pal-absent-Lys-, Asn-absent-absent-Lys, Asn-Pyal-absent-absent, and Gly-PyEA-absent-absent.

[0232] In the twenty-sixth group of embodiments, the compound of formula (I) is R1 is H or acetyl and is bonded to the amino functional group of X1, X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Dab, Dad, Dap and is bonded to X11 via an amide bond, X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Gln-Cys, Cys-Asn-Thr-Wim-Gln-Cys, Cys-Asn-Thr-Trp-Lys(Ac)-Cys, Cys-Asn-Thr-Wim-Lys(Ac)-Cys, Cys-Nmn-Thr-Trp-Gln-Cys, Abu-Asn-Thr-Trp-Lys(Ac)-Cys, Abu-Asn-Thr-Wim-Lys(Ac)-Cys and Abu-Asn-Thr-Wme-Leu-Cys, selected from X2-Q-X7 is Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond), or Abu-Q-Cys (Q is a thioether bond), or Glu-Q-Thr (Q is an ester bond), selected from the group of X8-X9-X10 is Yde-Nal-Aib, Yde-Nal-Mle, Yde-Nal-Thp, Yde-Nal-Mkdm, Yde-Nal-Mly, Yme-Nal-Aib, Yae-Nal-Mle, Yae-Nal-Thp, Yme-Nal and Yde-Nal-Aib, selected from the group of X11 is an amino acid residue selected from the residues of Asp, Glu, Kme and Lys and is bonded to X1 via an amide bond, X12-X13-X14-X15 is selected from the group consisting of Asn-Asn-absent-absent, Asn-Gly-absent-absent, Asn-d-Leu-absent-absent, Ala-Gly-absent-absent, Ala-d-Leu-absent-absent, Asn-His-absent-absent, Ser-His-absent-absent, Asn-Pal-absent-absent, Asn-Pal-Sar-absent, Asn-Pal-Sar-Lys, Asn-Pal-Ile-absent, Asn-Asn-Ile-absent, Asn-His-Sar-absent, Asn-His-Bal-absent, Asn-His-Mep-absent, Ser-Pal-Sar-absent, Ala-Pal-Sar-absent, Asn-Pal-absent-Lys, Asn-absent-absent-Lys, Asn-Pyal-absent-absent, and Gly-PyEA-absent-absent, R2 is absent or is -NH2, -OH or -N(C2H5)2, or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0233] In the 27th group of embodiments, the compound of formula (I) R1 is H or acetyl and is bonded to the amino function of X1, X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Dab, Dad, Dap and is bonded to X11 via an amide bond, X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Gln-Cys, Cys-Asn-Thr-Wim-Gln-Cys, Cys-Asn-Thr-Trp-Lys(Ac)-Cys, Cys-Asn-Thr-Wim-Lys(Ac)-Cys, Cys-Nmn-Thr-Trp-Gln-Cys, Abu-Asn-Thr-Trp-Lys(Ac)-Cys, Abu-Asn-Thr-Wim-Lys(AC)-Cys and selected from Abu-Asn-Thr-Wme-Leu-Cys, X2-Q-X7 is Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond), or Abu-Q-Cys (Q is a thioether bond), or selected from the group of Glu-Q-Thr (Q is an ester bond), X8-X9-X10 is selected from the group of Yde-Nal-Aib, Yde-Nal-Mle, Yde-Nal-Thp, Yde-Nal-Mkdm, Yde-Nal-Mly, Yme-Nal-Aib, Yae-Nal-Mle, Yme-Nal and selected from the group of Yde-Nal-Aib, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme and Lys, which is bonded to X1 via an amide bond, X12-X13-X14-X15 is selected from the group of Asn-Asn-absent-absent-, Asn-Gly-absent-absent-, Asn-d-Leu-absent-absent-, Ala-Gly-absent-absent-, Ala-d-Leu-absent-absent-, Asn-His-absent-absent-, Ser-His-absent-absent-, Asn-Pal-absent-absent-, Asn-Pal-Sar-absent-, Asn-Pal-Sar-Lys, Asn-Pal-Ile-absent-, Asn-Asn-Ile-absent-, Asn-His-Sar-absent-, Asn-His-Bal-absent-, Asn-His-Mep-absent, Ser-Pal-Sar-absent-, Ala-Pal-Sar-absent-, Asn-Pal-absent-Lys-, Asn-absent-absent-Lys, Asn-Pyal-absent-absent, and Gly-PyEA-absent-absent, R2 is a compound that is absent or is -NH2, -OH or -N(C2H5)2, or a salt or solvate thereof, A compound of formula (I), or a salt or solvate thereof, which inhibits the binding of the compound of formula (I) to the interleukin-23 receptor of interleukin-23.

[0234] In a twenty-eighth group of embodiments, the compound of formula (I) is R1 is H or acetyl, and is bonded to the amino functional group of X1, X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Dab, Dad, Dap, and is bonded to X11 via an amide bond, X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Gln-Cys, Cys-Asn-Thr-Wim-Gln-Cys, Cys-Asn-Thr-Trp-Lys(Ac)-Cys, Cys-Asn-Thr-Wim-Lys(Ac)-Cys, Cys-Nmn-Thr-Trp-Gln-Cys, Abu-Asn-Thr-Trp-Lys(Ac)-Cys, selected from Abu-Asn-Thr-Wme-Leu-Cys, X2-Q-X7 is Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond), or Abu-Q-Cys (Q is a thioether bond), or selected from the group of Glu-Q-Thr (Q is an ester bond), X8-X9-X10 is selected from the group of Yde-Nal-Aib, Yde-Nal-Mle, Yde-Nal-Thp, Yde-Nal-Mkdm, Yde-Nal-Mly, Yme-Nal-Aib, Yae-Nal-Mle, Yae-Nal-Thp, Yme-Nal and selected from the group of Yde-Nal-Aib, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme and Lys, and is bonded to X1 via an amide bond, X12-X13-X14-X15 is selected from the group of Asn-Asn-absent-absent-, Asn-Gly-absent-absent-, Asn-d-Leu-absent-absent-, Ala-Gly-absent-absent-, Ala-d-Leu-absent-absent-, Asn-His-absent-absent-, Ser-His-absent-absent-, Asn-Pal-absent-absent-, Asn-Pal-Sar-absent-, Asn-Pal-Sar-Lys, Asn-Pal-Ile-absent-, Asn-Asn-Ile-absent-, Asn-His-Sar-absent-, Asn-His-Bal-absent-, Asn-His-Mep-absent, Ser-Pal-Sar-absent-, Ala-Pal-Sar-absent-, Asn-Pal-absent-Lys-, Asn-absent-absent-Lys, Asn-Pyal-absent-absent, and Gly-PyEA-absent-absent, R2 is absent or is -NH2, -OH or -N(C2H5)2, a compound, or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0235] In the 29th group of embodiments, the compound of formula (I) R1 is H or acetyl and is bonded to the amino functional group of X1, X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Dab, Dad, Dap, and is bonded to X11 via an amide bond, X2-X3-X5-X6-X7 is Cys-Lys(αAc)-Trp-Gln-Cys, Cys-Lys(αAc)-Wim-Gln-Cys, Cys-Lys(αAc)-Trp-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Lys(Ac)-Cys, Cys-Ndmk-Trp-Lys(Ac)-Cys, selected from Cys-Ndmk-Wim-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Leu-Cys, Nmc-Lys(αAc)-Wim-Leu-Cys, selected from Cys-Apt-Trp-Gln-Cys, Abu-Lys(αAc)-Trp-Lys(Ac)-Cys, Abu-Lys(αAc)-Wim-Lys(Ac)-Cys, and selected from Glu-Apt-Trp-Gln-Thr, X4 is absent, X2-Q-X7 is selected from Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond) or Abu-Q-Cys (Q is a thioether bond), or selected from Glu-Q-Thr (Q is an ester bond), X8-X9-X10 is selected from the group consisting of Yde-Nal-Aib, Yde-Nal-Mle, Yde-Nal-Thp, Yde-Nal-Mkdm, Yde-Nal-Mly, Yme-Nal-Aib, Yae-Nal-Mle, Yae-Nal-Thp, Yme-Nal and Yde-Nal-Aib, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme and Lys, and is bonded to X1 via an amide bond, X12-X13-X14-X15 is Selected from the group consisting of Asn-Asn-absent-absent, Asn-Gly-absent-absent, Asn-d-Leu-absent-absent, Ala-Gly-absent-absent, Ala-d-Leu-absent-absent, Asn-His-absent-absent, Ser-His-absent-absent, Asn-Pal-absent-absent, Asn-Pal-Sar-absent, Asn-Pal-Sar-Lys, Asn-Pal-Ile-absent, Asn-Asn-Ile-absent, Asn-His-Sar-absent, Asn-His-Bal-absent, Asn-His-Mep-absent, Ser-Pal-Sar-absent, Ala-Pal-Sar-absent, Asn-Pal-absent-Lys, Asn-absent-absent-Lys, Asn-Pyal-absent-absent, and Gly-PyEA-absent-absent, R2 is absent or is -NH2, -OH or -N(C2H5)2, a compound, or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0236] In a 30th group of embodiments, the compound of formula (I) R1 is H or acetyl, bonded to the amino functionality of X1, X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Dab, Dad, Dap, and is bonded to X11 via an amide bond, X2-X3-X5-X6-X7 is Cys-Lys(αAc)-Trp-Gln-Cys, Cys-Lys(αAc)-Wim-Gln-Cys, Cys-Lys(αAc)-Trp-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Lys(Ac)-Cys, Cys-Ndmk-Trp-Lys(Ac)-Cys, selected from Cys-Ndmk-Wim-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Leu-Cys, Nmc-Lys(αAc)-Wim-Leu-Cys, selected from Cys-Apt-Trp-Gln-Cys, Abu-Lys(αAc)-Trp-Lys(Ac)-Cys, Abu-Lys(αAc)-Wim-Lys(Ac)-Cys, and selected from Glu-Apt-Trp-Gln-Thr, X4 is absent, X2-Q-X7 is Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond) or Abu-Q-Cys (Q is a thioether bond), or selected from Glu-Q-Thr (Q is an ester bond), X8-X9-X10 is selected from the group of Yde-Nal-Aib, Yde-Nal-Mle, Yde-Nal-Mkdm, Yde-Nal-Mly, Yme-Nal-Aib, Yae-Nal-Mle, Yae-Nal-Thp, Yme-Nal and Yde-Nal-Aib, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme and Lys, and is bound to X1 via an amide bond, X12-X13-X14-X15 is selected from the group of Asn-Asn-absent-absent-, Asn-Gly-absent-absent-, Asn-d-Leu-absent-absent-, Ala-Gly-absent-absent-, Ala-d-Leu-absent-absent-, Asn-His-absent-absent-, Ser-His-absent-absent-, Asn-Pal-absent-absent-, Asn-Pal-Sar-absent-, Asn-Pal-Sar-Lys, Asn-Pal-Ile-absent-, Asn-Asn-Ile-absent-, Asn-His-Sar-absent-, Asn-His-Bal-absent-, Asn-His-Mep-absent, Ser-Pal-Sar-absent-, Ala-Pal-Sar-absent-, Asn-Pal-absent-Lys, Asn-absent-absent-Lys, Asn-Pyal-absent-absent, and Gly-PyEA-absent-absent, R2 is absent or is -NH2, -OH or -N(C2H5)2, a compound, or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0237] In the 31st group of embodiments, the compound of formula (I) R1 is H or acetyl, bonded to the amino functional group of X1, X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Dab, Dad, Dap, and is bonded to X11 via an amide bond, X2-X3-X5-X6-X7 is Cys-Lys(αAc)-Trp-Gln-Cys, Cys-Lys(αAc)-Wim-Gln-Cys, Cys-Lys(αAc)-Trp-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Lys(Ac)-Cys, Cys-Ndmk-Trp-Lys(Ac)-Cys, selected from Cys-Ndmk-Wim-Lys(Ac)-Cys, Cys-Lys(αAc)-Wim-Leu-Cys, Nmc-Lys(αAc)-Wim-Leu-Cys, selected from Cys-Apt-Trp-Gln-Cys, Abu-Lys(αAc)-Trp-Lys(Ac)-Cys, selected from Glu-Apt-Trp-Gln-Thr, X4 is absent, X2-Q-X7 is Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond) or Abu-Q-Cys (Q is a thioether bond), or selected from Glu-Q-Thr (Q is an ester bond), X8-X9-X10 is selected from the group consisting of Yde-Nal-Aib, Yde-Nal-Mle, Yde-Nal-Thp, Yde-Nal-Mkdm, Yde-Nal-Mly, Yme-Nal-Aib, Yae-Nal-Mle, Yae-Nal-Thp, Yme-Nal and Yde-Nal-Aib, X11 is an amino acid residue selected from the residues of Asp, Glu, Kme and Lys, and is linked to X1 via an amide bond, X12-X13-X14-X15 is selected from the group consisting of Asn-Asn-absent-absent-, Asn-Gly-absent-absent-, Asn-d-Leu-absent-absent-, Ala-Gly-absent-absent-, Ala-d-Leu-absent-absent-, Asn-His-absent-absent-, Ser-His-absent-absent-, Asn-Pal-absent-absent-, Asn-Pal-Sar-absent-, Asn-Pal-Sar-Lys, Asn-Pal-Ile-absent-, Asn-Asn-Ile-absent-, Asn-His-Sar-absent-, Asn-His-Bal-absent-, Asn-His-Mep-absent, Ser-Pal-Sar-absent-, Ala-Pal-Sar-absent-, Asn-Pal-absent-Lys, Asn-absent-absent-Lys, Asn-Pyal-absent-absent, and Gly-PyEA-absent-absent; R2 is absent or is -NH2, -OH or -N(C2H5)2, a compound, or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0238] The compound of formula (Ia) In some embodiments, the peptide compounds described herein include one or more half-life extending moieties and / or a plurality of linker moieties attached to the peptide.

[0239] Formula (Ia)

Chemical formula

[0240] In some embodiments, the compound of formula (Ia) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0241] The embodiments described for R1, X1-X15 and R2 of formula (I) also apply to compounds of formula (Ia) in which at least one of X10 and X15 is functionalized as disclosed herein.

[0242] In some embodiments, for the compound of formula (Ia), X2 is an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and the corresponding d-forms thereof, and X8 is an amino acid residue selected from the amino acid residues of Yme, Tyr, Trp and Yde, or or, an amino acid residue selected from the amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and the corresponding d-forms thereof, and X8 is an amino acid residue selected from the amino acid residues of Yme, Tyr, TrP, Yde and Yae.

[0243] In some embodiments, for the compound of formula (Ia), when X2 is Abu or its corresponding d-form, X8 may not be the amino acid residue of Yae.

[0244] In some embodiments, for the compound of formula (Ia), when X8 is Yae, X2 may not be the amino acid residue of Abu or its corresponding d-form.

[0245] A first group of embodiments of the compounds of formula (Ia) is - X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad and Dap, and is bonded to X11 via an amide bond, or Alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond. -R1 is absent or When X1 is a residue selected from the residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C1-C4-alkyl or acetyl, and is bonded to the amino functional group of X1. -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and their corresponding d-forms. -X7 is an amino acid residue selected from Cys, Glu, Asp, Thr and Abu, and their corresponding d-forms. X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond. -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc). -X4 is absent or is an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr. -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl. -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe. -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp and Yde. -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp. -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, -X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, -X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, PyAl, PyEA, His, Hme, Val, and their corresponding d-forms, -X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH or -N(C2H5)2, The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, At least one of X10 and X15 is an amino acid residue having a side chain with an -NH2 group, and the -NH2 side chain group is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5 or R5, where R5 is a moiety optionally containing up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O, S and P, or a salt or solvate thereof, The compound of formula (Ia) may be one that inhibits the binding of interleukin-23 to the interleukin-23 receptor, or a salt or solvate thereof.

[0246] A second group of embodiments of the compound of formula (Ia) is -X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad, and Dap, and is bonded to X11 via an amide bond, or alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is absent or when X1 is a residue selected from the residues of Ahx, Aoa, Apt, Lys, Dab, and Dap, R1 is H, C1-C4-alkyl, or acetyl, and is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, and Thr, and their corresponding d-forms, -X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr, and Abu, and their corresponding d-forms, X2 and X7 are bonded to each other via Q, where Q is a disulfide bond, a thioether bond, or an ester bond, -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk, and Lys(αAc), -X4 is absent or is an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm, and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp, and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde, and Yae, -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is bonded to -X1 via an amide bond, -X12 is either absent or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, -X13 is either absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, PyAl, PyEA, His, Hme, Val, and amino acid residues selected from the corresponding d-forms thereof, -X14 is either absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy and Hme, -X15 is either absent or is an amino acid residue of Lys, -R2 is either absent or is -NH2, -OH or -N(C2H5)2, The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, At least one of X10 and X15 is an amino acid residue having a side chain with an -NH2 group, and the -NH2 side chain group is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5 or R5, where R5 is a moiety optionally containing up to 50 or up to 100 carbon atoms, and optionally heteroatoms selected from halogen, N, O, S and P, or a salt or solvate thereof, The compound of formula (Ia) may be one that inhibits the binding of interleukin-23 to the interleukin-23 receptor, or a salt or solvate thereof.

[0247] In some embodiments, at least one of X10 and X15 is an amino acid residue having a side chain with an -NH2 group, and the -NH2 side chain group is functionalized by -C(O)-R5, where R5 may be a moiety containing up to 50 or up to 100 carbon atoms, and optionally a heteroatom selected from halogen, N, O, S, and P.

[0248] In one embodiment, X10 or X15 is an amino acid residue having a functionalized -NH2 side chain group, such as functionalized Lys, Orn, Mly, Dab, or Dap, or an amino acid residue having functionalized Lys or Mly.

[0249] An amino acid residue having an -NH2 side chain group, such as Lys, Orn, Mly, Dab, or Dap, may be functionalized in that at least one H atom of the -NH2 side chain group is substituted with -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5, or R5, such as -C(O)-R5, where R5 may be a moiety containing up to 50 or up to 100 carbon atoms, and optionally a heteroatom selected from halogen, N, O, S, and P.

[0250] In certain embodiments, R5 may include a lipophilic moiety, such as an acyclic straight-chain or branched saturated hydrocarbon group, and R5 may be, for example, an acyclic straight-chain or branched (C4~C 30 ) saturated or unsaturated hydrocarbon group, and / or a cyclic saturated, unsaturated, or aromatic group, such as a monocyclic, bicyclic, or tricyclic group containing 4 to 14 carbon atoms and 0, 1, or 2 heteroatoms selected from N, O, and S, such as cyclohexyl, phenyl, biphenyl, chromanyl, phenanthrenyl, or naphthyl, and the acyclic or cyclic group may be unsubstituted or substituted, for example, with halogen, -OH, and / or CO2H.

[0251] In some embodiments, R5 is a lipophilic moiety, such as an acyclic straight-chain or branched-chain (C 12 ~C 22) It may contain a saturated or unsaturated hydrocarbon group. The lipophilic moiety may be linked to the -NH2 side chain group by linkers in all stereoisomeric forms, for example, linkers containing one or more, for example, two amino acid linker groups, for example, γ-aminobutyric acid (GABA), ε-aminohexanoic acid (ε-Ahx), γ-Glu and / or β-Ala. In one embodiment, the lipophilic moiety is linked to the -NH2 side chain group by a linker. In another embodiment, the lipophilic moiety is directly linked to the -NH2 side chain group. Specific examples of amino acid linker groups are (β-Ala) 1-4 , (γ-Glu) 1-4 , (ε-Ahx) 1-4 or (GABA) 1-4 . Embodiments of the amino acid linker group are β-Ala, γ-Glu, β-Ala-β-Ala and γ-Glu-γ-Glu.

[0252] Specific examples of the -C(O)-R5 group are listed in Table 2 below, (S)-4-carboxy-4-hexadecanoylamino-butyryl-, (S)-4-carboxy-4-octadecanoylamino-butyryl-, 4-hexadecanoylamino-butyryl-, 4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, 4-octadecanoylamino-butyryl-, 4-((Z)-octadec-9-enoylamino)-butyryl-, 6-[(4,4-diphenyl-cyclohexyloxy)-hydroxy-phosphoryloxy]-hexanoyl-, hexadecanoyl-, (S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyryl-, (S)-4-carboxy-4-{3-[3-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-propionylamino]-propionylamino}-butyryl-, (S)-4-carboxy-4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, (S)-4-carboxy-4-((9Z,12Z)-octadeca-9,12-dienoylamino)-butyryl-, (S)-4-carboxy-4-[6-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-hexanoylamino]-butyryl-, (S)-4-carboxy-4-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-butyryl-, (S)-4-carboxy-4-tetradecanoylamino-butyryl-, (S)-4-(11-benzyloxycarbonyl-undecanoylamino)-4-carboxy-butyryl-, (S)-4-carboxy-4-[11-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxy-hexylcarbamoyl)-undecanoylamino]-butyryl-, (S)-4-carboxy-4-((Z)-octadec-9-enoylamino)-butyryl-,(S)-4-Carboxy-4-(4-dodecyloxy-benzoylamino)-butyryl-, (S)-4-carboxy-4-henicosanoylamino-butyryl-, (S)-4-carboxy-4-docosanoylamino-butyryl-, (S)-4-carboxy-4-((Z)-nonadec-10-enoylamino)-butyryl-, (S)-4-carboxy-4-(4-decyloxy-benzoylamino)-butyryl-, (S)-4-carboxy-4-[(4’-octyloxy-biphenyl-4-carbonyl)amino]-butyryl-, (S)-4-carboxy-4-(12-phenyl-dodecanoylamino)-butyryl-, (S)-4-carboxy-4-icosanoylamino-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-hexadecanoylbutyrylamino-butyrylamino)-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-octadecanoylbutyrylamino-butyrylamino)-butyryl-, 3-(3-octadecanoylamino-propionylamino)-propionyl-, 3-(3-hexadecanoylamino-propionylamino)-propionyl-, 3-hexadecanoylamino-propionyl-, (S)-4-carboxy-4-[(R)-4-((3R,5S,7R,8R,9R,10S,12S,13R,14R,17R)-3,7,12-trihydroxy-8,10,13-trimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-carboxy-4-[(R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-carboxy-4-((9S,10R)-9,10,16-trihydroxy-hexadecanoylamino)-butyryl-, tetradecanoyl-, 11-carboxy-undecanoyl-, 11-benzyloxycarbonyl-undecanoyl-, (S)-4-carboxy-4-((S)-4-carboxy-4-tetradecanoylamino-butyrylamino)-butyryl-, 6-[hydroxy-(naphthalen-2-yloxy)-phosphoryloxy]-hexanoyl-,6-[Hydroxy-(5-phenyl-pentyloxy)-phosphoryloxy]-hexanoyl-, 4-(naphthalene-2-sulfonylamino)-4-oxo-butyryl-, 4-(biphenyl-4-sulfonylamino)-4-oxo-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-acetylamino]-butyryl-, (S)-4-carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-,(S)-4-Carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetyl, (S)-4-carboxy-4-((S)-4-carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-butyrylamino}-butyrylamino)-butyryl, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(16-1H-tetrazol-5-yl-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(16-carboxy-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxy-phenoxy)-decanoylamino]-butyrylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(7-carboxy-heptanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-,(S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(11-carboxy-undecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(13-carboxy-tridecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, and (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl- are selected from the group consisting of.,

[0253] Other specific examples of the -C(O)-R5 group are tetradecanoyl, hexadecanoyl and 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-.

[0254] Other specific examples of the -C(O)-R5 group are listed in Table 2 as Myri, Palm and Sema.

[0255] Further embodiments are stereoisomers, for example, either enantiomers of these groups, the S - enantiomer or the R - enantiomer. The term "R" in Table 2 is intended to mean the bonding site of - C(O) - R5 in the peptide backbone, i.e., for example, the ε - amino group of Lys or Mly.

[0256] [Table 14]

[0257] [Table 15]

[0258] [Table 16]

[0259] [Table 17]

[0260] [Table 18]

[0261] [Table 19]

[0262] [Table 20]

[0263] [Table 21]

[0264] [Table 22]

[0265]

Table 23

[0266]

Table 24

[0267]

Table 25

[0268]

Table 26

[0269]

Table 27

[0270] According to one embodiment, R5 is (S)-4-carboxy-4-hexadecanoylamino-butyryl (γE-x53), (S)-4-carboxy-4-octadecanoylamino-butyryl (γE-x70), 4-hexadecanoylamino-butyryl (GABA-x53), 4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-(GABA-x60), 4-octadecanoylamino-butyryl (GABA-x70), 4-((Z)-octadec-9-enoylamino)-butyryl (GABA-x74), 6-[(4,4-diphenyl-cyclohexyloxy)-hydroxy-phosphoryloxy]-hexanoyl (Phospho1), hexadecanoyl (x53),), tetradecanoyl (x69), (S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyryl (x52), (S)-4-carboxy-4-{3-[3-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-propionylamino]-propionylamino}-butyryl (γE-x59), (S)-4-carboxy-4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl (γE-x60), (S)-4-carboxy-4-((9Z,12Z)-octadeca-9,12-dienoylamino)-butyryl (γE-x61), (S)-4-carboxy-4-[6-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-hexanoylamino]-butyryl (γE-x64), (S)-4-carboxy-4-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-butyryl (γE-x65), (S)-4-carboxy-4-tetradecanoylamino-butyryl (γE-x69), (S)-4-(11-benzyloxycarbonyl-undecanoylamino)-4-carboxy-butyryl (γE-x72), (S)-4-carboxy-4-[11-((2S,3R,4R,((5R)-2,3,4,5,6-pentahydroxy-hexylcarbamoyl)-undecanoylamino]-butyryl (γE-x73), (S)-4-carboxy-4-((Z)-octadec-9-enoyl amino)-butyryl (γE-x74), (S)-4-carboxy-4-(4-dodecyloxy-benzoylamino)-butyryl (γE-x75), (S)-4-carboxy-4-henicosanoylamino-butyryl (γE-x76), (S)-4-carboxy-4-docosanoylamino-butyryl (γE-x77), (S)-4-carboxy-4-((Z)-nonadec-10-enoyl amino)-butyryl (γE-x79), (S)-4-carboxy-4-(4-decyloxy-benzoylamino)-butyryl (γE-x80), (S)-4-carboxy-4-[(4'-octyloxy-biphenyl-4-carbonyl)-amino]-butyryl (γE-x81), (S)-4-carboxy-4-(12-phenyl-dodecanoylamino)-butyryl (γE-x82), (S)-4-carboxy-4-icosanoylamino-butyryl (γE-x95), (S)-4-carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl (γE-γE-x53), (S)-4-carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl (γE-E-x70), and 3-(3-octadecanoylamino-propionylamino)-propionyl (β-Ala-β-Ala-x70) is selected from the group consisting of.,

[0271] According to another embodiment, R5 is selected from the group consisting of (S)-4-carboxy-4-octadecanoylamino-butyryl (γE-x70), (S)-4-carboxy-4-hexadecanoylamino-butyryl (γE-x53) and hexadecanoyl (x53).

[0272] According to yet another embodiment, R5 is (S)-4-carboxy-4-hexadecanoylamino-butyryl (γE-x53).

[0273] In some embodiments, the 10th or 15th X represents Lys or Mly. According to some embodiments, Lys or Mly at the 10th X and Lys at the 15th X are functionalized, for example, with the above -C(O)R5 group.

[0274] In other embodiments, the 15th X is absent, and the 10th X is Mly functionalized with -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5, or R5, for example, functionalized with -C(O)-R5, and R5 is as defined above.

[0275] In other embodiments, the 10th X is not functionalized, and the 15th X is Lys functionalized with -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5, or R5, for example, functionalized with -C(O)-R5, and R5 is as defined above.

[0276] In other embodiments, the 10th X is not functionalized, the 14th X is absent, and the 15th X is Lys functionalized with -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5, or R5, for example, functionalized with -C(O)-R5, and R5 is as defined above.

[0277] In some embodiments, X15 is absent, X10 is Mly-functionalized with C(O)-R5, and R5 is (S)-4-carboxy-4-hexadecanoylamino-butyryl (γE-x53), (S)-4-carboxy-4-octadecanoylamino-butyryl (γE-x70), 4-hexadecanoylamino-butyryl (GABA-x53), 4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-(GABA-x60), 4-octadecanoylamino-butyryl (GABA-x70), 4-((Z)-octadec-9-enoylamino)-butyryl (GABA-x74), 6-[(4,4-diphenyl-cyclohexyloxy)-hydroxy-phosphoryloxy]-hexanoyl (Phospho1), hexadecanoyl (x53), (S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyryl (x52), (S)-4-carboxy-4-{3-[3-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-propionylamino]-propionylamino}-butyryl (γE-x59), (S)-4-carboxy-4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl (γE-x60), (S)-4-carboxy-4-((9Z,12Z)-octadeca-9,12-dienoylamino)-butyryl (γE-x61), (S)-4-carboxy-4-[6-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-hexanoylamino]-butyryl (γE-x64), (S)-4-carboxy-4-((2S,3R,4S,5R)-5-carboxy-2,3,4,Selected from the group consisting of 5-tetrahydroxy-pentanoylamino)-butyryl(γE-x65), (S)-4-carboxy-4-tetradecanoylamino-butyryl(γE-x69), (S)-4-(11-benzyloxycarbonyl-undecanoylamino)-4-carboxy-butyryl(γE-x72), (S)-4-carboxy-4-[11-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxy-hexylcarbamoyl)-undecanoylamino]-butyryl(γE-x73), (S)-4-carboxy-4-((Z)-octadec-9-enoylamino)-butyryl(γE-x74), (S)-4-carboxy-4-(4-dodecyloxy-benzoylamino)-butyryl(γE-x75), (S)-4-carboxy-4-henicosanoylamino-butyryl(γE-x76), (S)-4-carboxy-4-docosanoylamino-butyryl(γE-x77), (S)-4-carboxy-4-((Z)-nonadec-10-enoylamino)-butyryl(γE-x79), (S)-4-carboxy-4-(4-decyloxy-benzoylamino)-butyryl(γE-x80), (S)-4-carboxy-4-[(4’-octyloxy-biphenyl-4-carbonyl)-amino]-butyryl(γE-x81), (S)-4-carboxy-4-(12-phenyl-dodecanoylamino)-butyryl(γE-x82), (S)-4-carboxy-4-icosanoylamino-butyryl(γE-x95), (S)-4-carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl(γE-γE-x53), (S)-4-carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl(γE-γE-x70), and 3-(3-octadecanoylamino-propionylamino)-propionyl(β-Ala-β-Ala-x70).

[0278] In some embodiments, X10 is not functionalized and X15 is Lys functionalized with C(O)-R5, where R5 is (S)-4-carboxy-4-hexadecanoylamino-butyryl (γE-x53), (S)-4-carboxy-4-octadecanoylamino-butyryl (γE-x70), 4-hexadecanoylamino-butyryl (GABA-x53), 4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-(GABA-x60), 4-octadecanoylamino-butyryl (GABA-x70), 4-(Z)-octadec-9-enoylamino)-butyryl (GABA-x74), 6-[(4,4-diphenyl-cyclohexyloxy)-hydroxy-phosphoryloxy]-hexanoyl (Phospho1), hexadecanoyl (x53), (S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyryl (x52), (S)-4-carboxy-4-{3-[3-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-propionylamino]-propionylamino}-butyryl (γE-x59), (S)-4-carboxy-4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl (γE-x60), (S)-4-carboxy-4-((9Z,12Z)-octadeca-9,12-dienoylamino)-butyryl (γE-x61), (S)-4-carboxy-4-[6-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-hexanoylamino]-butyryl (γE-x64), (S)-4-carboxy-4-((2S,3R,4S,5R)-5-carboxy-2,3,4,(5-Tetrahydroxy-pentanoylamino)-butyryl (γE-x65), (S)-4-Carboxy-4-tetradecanoylamino-butyryl (γE-x69), (S)-4-(11-Benzyloxycarbonyl-undecanoylamino)-4-carboxy-butyryl (γE-x72), (S)-4-Carboxy-4-[11-((2S,3R,4R,5R)-2,3,4,5,6-Pentahydroxy-hexylcarbamoyl)-undecanoylamino]-butyryl (γE-x73), (S)-4-Carboxy-4-((Z)-Octadec-9-enoylamino)-butyryl (γE-x74), (S)-4-Carboxy-4-(4-Dodecyloxy-benzoylamino)-butyryl (γE-x75), (S)-4-Carboxy-4-henicosanoylamino-butyryl (γE-x76), (S)-4-Carboxy-4-docosanoylamino-butyryl (γE-x77), (S)-4-Carboxy-4-((Z)-Nonadec-10-enoylamino)-butyryl (γE-x79), (S)-4-Carboxy-4-(4-Decyloxy-benzoylamino)-butyryl (γE-x80), (S)-4-Carboxy-4-[(4’-Octyloxy-biphenyl-4-carbonyl)-amino]-butyryl (γE-x81), (S)-4-Carboxy-4-(12-Phenyl-dodecanoylamino)-butyryl (γE-x82), (S)-4-Carboxy-4-icosanoylamino-butyryl (γE-x95), (S)-4-Carboxy-4-((S)-4-Carboxy-4-hexadecanoylamino-butyrylamino)-butyryl (γE-γE-x53), (S)-4-Carboxy-4-((S)-4-Carboxy-4-octadecanoylamino-butyrylamino)-butyryl (γE-γE-x70), and 3-(3-Octadecanoylamino-propionylamino)-propionyl (β-Ala-β-Ala-x70) are selected from the group consisting of.,

[0279] Specific examples of the peptide compounds of formula (I) and formula (Ia) are the compounds of SEQ ID NOs: 1 to 158, or salts or solvates thereof.,

[0280] Specific examples of the peptide compound of formula (I) are compounds of SEQ ID NOs: 1 to 66, 68 to 70, 72 to 74, 76 to 82, 84 to 95, 98, 102 to 106, 108 to 158, or salts or solvates thereof.

[0281] Specific examples of the peptide compound of formula (Ia) are compounds of SEQ ID NOs: 67, 71, 75, 83, 96, 97, 99, 100, 101, 107, and 108, or salts or solvates thereof.

[0282] In some embodiments, the compounds of the present disclosure are selected from compounds of SEQ ID NOs: 1 to 158, or salts or solvates thereof.

[0283] In some embodiments, the compounds of the present disclosure are selected from compounds of SEQ ID NOs: 1 to 74, 101 to 106, 115, 116, 122, 126, 127, and 149 to 158, or salts or solvates thereof.

[0284] In some embodiments, the compounds of the present disclosure are selected from compounds of SEQ ID NOs: 75 to 100, 107 to 114, 117 to 121, 123 to 125, and 128 to 148, or salts or solvates thereof.

[0285] In some embodiments, the compounds of the present disclosure are selected from compounds of SEQ ID NOs: 1 to 70, 72 to 74, 101 to 106, 115, 116, 122, 126, 127, and 149 to 158, or salts or solvates thereof.

[0286] In some embodiments, the compounds of the present disclosure are selected from compounds of SEQ ID NOs: 71, 75 to 100, 107 to 114, 117 to 121, 123 to 125, and 128 to 148, or salts or solvates thereof.

[0287] In some embodiments, the compounds of the present disclosure are selected from compounds of SEQ ID NOs: 1 to 74, 102 to 106, 122, 126, 127, and 149 to 158, or salts or solvates thereof.

[0288] In some embodiments, the compounds of the present disclosure are selected from the compounds of SEQ ID NOs: 75-101, 107-121, 123-125, and 128-148, or salts or solvates thereof.

[0289] In some embodiments, the compounds of the present disclosure are selected from the compounds of SEQ ID NOs: 1-74, 102-106, 122, 126, and 149-158, or salts or solvates thereof.

[0290] In some embodiments, the compounds of the present disclosure are selected from the compounds of SEQ ID NOs: 75-101, 107-121, 123-127, and 128-148, or salts or solvates thereof.

[0291] In some embodiments, the compounds of the present disclosure are selected from the compounds of SEQ ID NOs: 1-38, 40-74, 108-106, 126, 127, 149, 151, 152, and 154-158, or salts or solvates thereof.

[0292] In some embodiments, the compounds of the present disclosure are the compounds of SEQ ID NOs: 67, 71, 75, 83, 96, 97, 99, 100, 101, 107, and 108, or salts or solvates thereof.

[0293] In some embodiments, the compounds of the present disclosure are the compounds of SEQ ID NOs: 35, 66, 113, 128, 144, 146, 147, 147, 148, and 149, or salts or solvates thereof.

[0294] Table 3 shows the structures of the compounds of SEQ ID NOs: 1-158.

[0295]

Table 28

[0296]

Table 29

[0297]

Table 30

[0298]

Table 31

[0299]

Table 32

[0300]

Table 33

[0301] (@2) indicates the formation of an ester, thioether or disulfide bridge between amino acid residues.

[0302] (§1) indicates the formation of a lactam bridge between amino acid residues.

[0303] C(§3), Nmc(§3) or Abu(§3) and K[aAc](@3) indicate the formation of a peptide bond between the ε-NH2 group of K[aAc] and the C-terminus of C, Nmc or Abu.

[0304] [Ac] indicates the acetylation of R1 of the X1 amino acid residue or the acetylation of the amino acid side chain.

[0305] The compounds disclosed herein have a binding affinity for the interleukin 23 receptor determined using the method described in the examples (i.e., human ELISA IL23 / IL23R) of 100 nM or less (i.e., IC 50 ≦100 nM), or 50 nM or less (i.e., IC 50 ≦50.0 nM), or 10 nM or less (i.e., IC 50 ≦10.0 nM), and further 5 nM or less (i.e., IC 50 ≦5.0 nM).

[0306] As used herein, the term "activity" refers to the ability of a compound to inhibit the human interleukin-23 receptor. For example, as used herein, the term "activity" refers to the ability of a compound to stimulate intracellular STAT3 phosphorylation. Sometimes, instead of "activity", the terms "efficacy" or "in vitro efficacy" may also be referred to. Thus, "efficacy" is a measure of the ability of a compound to inhibit the interleukin-23 receptor in a cell-based assay. Numerically, it is represented as an "IC 50 value", which is the effective concentration of a compound that inhibits a 50% increase in the maximum response (e.g., the formation of phosphorylated STAT3) in a dose-response experiment.

[0307] The compounds disclosed herein have interleukin-23 receptor affinity. This term refers to the ability to bind to the interleukin-23 receptor and inhibit the signaling pathway that leads to Th17 cell activation or other physiological effects known in the art. For example, the compounds disclosed herein can be tested for interleukin-23 receptor affinity or activity using the assays described in the methods and results shown in Table 10 herein.

[0308] In a further embodiment, the compounds disclosed herein are sufficiently chemically stable in solutions of different pH values.

[0309] The compounds disclosed herein have a chemical stability with a relative purity loss of less than 30%, or less than 25% over 24 hours at 37°C in a solution of pH 1.2.

[0310] The compounds disclosed herein have a chemical stability with a relative purity loss of less than 5%, or less than 2% over 24 hours at 37°C in a solution of pH 6.5.

[0311] The compounds disclosed herein have a chemical stability with a relative purity loss of less than 5%, or less than 3% over 24 hours at 37°C in a solution of pH 7.4.

[0312] In a further embodiment, the compounds disclosed herein are sufficiently stable in the intestinal environment to achieve a pharmacological effect.

[0313] Peptide synthesis Those skilled in the art know various different methods for preparing peptides. These methods include, but are not limited to, synthetic approaches and recombinant gene expression. Thus, one method for preparing a peptide is synthesis in solution or on a solid support, followed by isolation and purification.

[0314] The method for preparing the compounds disclosed herein is solid-phase synthesis on a suitable resin. Solid-phase peptide synthesis is a well-established methodology (see, for example, Stewart and Young, Solid Phase Peptide Synthesis, Pierce Chemical Co., Rockford, Ill., 1984; E. Atherton and R. C. Sheppard, Solid Phase Peptide Synthesis. A Practical Approach, Oxford-IRL Press, New York, 1989). Solid-phase synthesis is initiated by attaching the carboxy terminus of an N-terminal protected amino acid to an inert solid support having a cleavable linker. This solid support can be any polymer that allows coupling of the first amino acid and can be, for example, a trityl resin, a chlorotrityl resin, a Wang resin, or a Rink resin if the linkage of the carboxy group (or carboxamide in the case of Rink resin) to the resin is acid-sensitive (when the Fmoc strategy is used). The polymeric support must be stable under the conditions used to deprotect the α-amino group during peptide synthesis.

[0315] After conjugating the first amino acid with its N-terminus protected to a solid support, the α-amino protecting group of this amino acid is removed. Subsequently, the remaining protected amino acids are coupled in the order represented by the peptide sequence, either sequentially or with pre-formed dipeptides, tripeptides or tetrapeptides, or with amino acid components having modified side chains, such as N-alpha-(9-fluorenylmethyloxycarbonyl)-N-epsilon-(N-alpha'-octadecanedionyl-t-butyl ester-L-glutamic acid alpha'-t-butyl ester-2-[2-[[2-[2-[2-(2-aminoethoxy)ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl)-L-lysine, (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-methyl-6-(tetradecanoylamino)hexanoic acid, or (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-(hexadecanoylamino)-2-methyl-hexanoic acid, using a suitable amide coupling reagent, such as BOP, HBTU, HATU or DIC (N,N'-diisopropylcarbodiimide) / HOBt (1-hydroxybenzotriazole), where BOP, HBTU and HATU are used with a tertiary amine base. Alternatively, the free N-terminus can be functionalized with a group other than an amino acid, such as a carboxylic acid.

[0316] Normally, the reactive side chain groups of the amino acids are protected with suitable protecting groups. This protecting group is removed after the desired peptide has been assembled. This protecting group is removed simultaneously with the cleavage of the desired product from the resin under the same conditions. The protecting groups and the procedures for introducing the protecting groups can be found in Protective Groups in Organic Synthesis, 3d ed., Greene, T.W. and Wuts, P.G.M., Wiley & Sons (New York: 1999).

[0317] In some cases, it may be desirable to have a side chain protecting group that can be selectively removed while leaving other side chain protecting groups intact. In this case, the liberated functional group can be selectively functionalized. For example, lysine can be protected with the ivDde ([1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl]) protecting group, which is labile to 4% hydrazine in a very nucleophilic base, such as DMF (dimethylformamide) (S.R. Chhabra et al., Tetrahedron Lett. 39, (1998), 1603). Thus, when the N-terminal amino group and all side chain functional groups are protected with acid-labile protecting groups, the ivDde group can be selectively removed using 4% hydrazine in DMF, and then the corresponding liberated amino group can be further modified, for example, by acylation. Alternatively, lysine can be conjugated with a protected amino acid, then the amino group of this amino acid can be deprotected, and the resulting another liberated amino group can be acylated or attached to a further amino acid.

[0318] Finally, the peptide is cleaved from the resin. This can be achieved using King's cocktail (D.S. King, C.G. Fields, G.B. Fields, Int. J. Peptide Protein Res. 36, 1990, 255 - 266) or a similar cleavage cocktail known to those skilled in the art. For example, EDT can be replaced with DODT, or a mixture of TIS, water, and TFA can be used. Then, the crude material can be purified by chromatography, such as preparative RP-HPLC, if necessary.

[0319] All starting materials such as amino acids and chemical substances were obtained from vendors. For example, (2S)-6-(tert-butoxycarbonylamino)-2-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoic acid was purchased from Fisher Scientific (eKat). Other suppliers are Bachem AG, Hauptstrasse 144, 4416 Bubendorf, Switzerland; Iris Biotech GmbH, Adalbert-Zoellner-Str1, 95615 Marktredwitz, Gyros Protein Technologies, Uppsala Science Park, Dag Hammarskjoeldsvaeg 54, SE-75183 Uppsala, Sweden; Thermo Fisher Scientific, 168 Third Avenue, Waltham, MA USA 02451.

[0320] Cyclization / Lactam Formation Methods for lactam bond formation are known to those skilled in the art. Exemplary methods are shown in the Examples. Unbonded amino acid residues homoserine (hSer) or homoserine (Br) may take the form of 2-aminobutyric acid (Abu) when involved in intramolecular bonds according to the present disclosure.

[0321] The synthesis of Sema is described in International Publication No. WO 2011 / 080102, which is incorporated by reference.

[0322] Potency As used herein, the term "potency" or "in vitro potency" is a measure of the ability of a compound to inactivate the interleukin-23 receptor in a cell-based assay. Numerically, it is expressed as an "IC 50 value", which is the effective concentration of a compound that induces a maximum half-maximal decrease in response (e.g., the state of intracellular STAT3) in a dose-response experiment.

[0323] Therapeutic Use The term "disease or disorder" refers to any pathological or unhealthy condition, particularly diseases related to the immune system such as ulcerative colitis, Crohn's disease, and psoriasis.

[0324] "Treat" or "treating" means administering to a subject a compound or composition, or a combination of compounds or compositions, to eliminate a disease or disorder in the subject, to inhibit or delay a disease or disorder in the subject, to inhibit or delay the onset of a new disease or disorder in the subject, to reduce the frequency or severity of symptoms and / or recurrence of a disease or disorder in a subject that currently or has in the past suffered from the disease or disorder, and / or to extend (i.e., increase) the lifespan of the subject. For example, the term "treating / treatment of a disease or disorder" includes curing a disease or disorder, or its symptoms, shortening the duration thereof, remission, delaying or inhibiting progression or worsening thereof.

[0325] "Prevent" or "preventing" means administering to a subject a compound or composition, or a combination of compounds or compositions, to inhibit or delay the onset of a disease or disorder in the subject.

[0326] The term "subject" according to the present disclosure means a subject to be treated, particularly a subject with a disease (also referred to as a "patient"), for example, a human, a non-human primate, or other animals, particularly mammals (e.g., cows, horses, pigs, sheep, goats, dogs, cats, rabbits), or rodents (e.g., mice, rats, guinea pigs, and hamsters). In one embodiment, the subject / patient is a human.

[0327] In certain embodiments, the present disclosure includes a method of inhibiting IL-23 signaling by a cell, the method comprising contacting IL-23 with a peptide compound disclosed herein. In certain embodiments, the cell is a mammalian cell. In certain embodiments, the method is performed in vitro or in vivo. In some embodiments, inhibition of IL-23 signaling can be assayed by measuring a change in phospho-STAT3 levels in the cell.

[0328] In some embodiments, inhibition of the binding of IL-23 to the IL-23R occurs in a particular organ or tissue of a subject, such as the stomach, small intestine, large intestine / colon, intestinal mucosa, lamina propria, Peyer's patches, mesenteric lymph nodes, or lymphatic vessels.

[0329] Further provided is the use of a compound of formula (I) or (Ia) of the present disclosure, or a composition comprising a compound of formula (I) or (Ia) of the present disclosure, in the preparation of a pharmaceutical composition for treating an autoimmune disease or an inflammatory disease.

[0330] The autoimmune disease or inflammatory disease can be, for example, an inflammatory bowel disease such as Crohn's disease and ulcerative colitis, psoriasis, psoriatic arthritis, and hidradenitis suppurativa.

[0331] In certain embodiments, the disease or disorder is an autoimmune inflammation and related diseases and disorders, such as multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease (IBD), juvenile IBD, adolescent IBD, Crohn's disease, sarcoidosis, systemic lupus erythematosus, ankylosing spondylitis (axial spondyloarthritis), psoriatic arthritis or psoriasis. In some embodiments, the disease or disorder is psoriasis (e.g., plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, palmoplantar pustulosis, plaque psoriasis, or erythrodermic psoriasis), atopic dermatitis, acne vulgaris, ulcerative colitis, Crohn's disease, celiac disease (nontropical sprue), enteropathy associated with seronegative spondyloarthropathy, microscopic colitis, collagenous colitis, eosinophilic gastroenteritis / esophagitis, radiation or chemotherapy associated colitis, colitis associated with congenital immune disorders such as leukocyte adhesion deficiency-1, chronic granulomatous disease, glycogen storage disease type lb, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Wiskott-Aldrich syndrome, pouchitis occurring after colectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-independent diabetes, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral enteric disease, pericholangitis, chronic bronchitis, chronic rhinosinusitis, asthma, uveitis, or graft-versus-host disease.

[0332] In further related embodiments, the disclosure includes a method of inhibiting gastrointestinal (GI) inflammation and / or neutrophil infiltration into the GI, the method comprising administering to a subject in need thereof a peptide compound disclosed herein.

[0333] Pharmaceutical composition The term "pharmaceutical composition" refers to a mixture containing components that are compatible when mixed and can be administered. A pharmaceutical composition may contain one or more pharmaceuticals. In addition, a pharmaceutical composition may contain carriers, buffers, acidifying agents, alkalizing agents, solvents, adjuvants, isotonic agents, emollients, bulking agents, preservatives, physical and chemical stabilizers, such as surfactants, antioxidants, and other components, whether these are regarded as active ingredients or inactive ingredients. Examples of preservatives are benzyl-type alcohols, or phenolic compounds such as phenol or m-cresol.

[0334] The pharmaceutical composition may comprise one or more compounds of the present disclosure and at least one pharmaceutically acceptable carrier.

[0335] "Pharmaceutically acceptable carrier" is a carrier that is physiologically acceptable (e.g., physiologically acceptable pH) while retaining the therapeutic properties of the administered substance. Pharmaceutically acceptable carriers, diluents or excipients refer to any kind of non-toxic solid, semi-solid or liquid filler, diluent, encapsulating material or formulation adjuvant.

[0336] Standard acceptable pharmaceutical carriers and their formulations are known to those skilled in the art and are described, for example, in Remington: The Science and Practice of Pharmacy, (20th ed.) ed. A.R. Gennaro A.R., 2000, Lippencott Williams & Wilkins and R.C. Rowe et al. (Ed), Handbook of Pharmaceutical excipients, PhP, May 2013 update. An example of a physiologically acceptable carrier is physiological saline.

[0337] The term "pharmaceutically acceptable salt" means a salt of the compounds disclosed herein that is safe and effective for use in mammals, for example, acetate salt, chloride salt, or sodium salt.

[0338] The term "solvate" means a complex of a compound or its salt disclosed herein with solvent molecules (e.g., organic solvent molecules) and / or water.

[0339] Examples of acceptable pharmaceutical carriers or diluents include those used in formulations suitable for oral, rectal, nasal, or parenteral (e.g., subcutaneous, intramuscular, intravenous, intradermal, and transdermal) administration.

[0340] In certain embodiments, the composition is administered orally, parenterally, intracisternally, intravaginally, intraperitoneally, rectally, topically (by powder, ointment, drops, suppository, or transdermal patch), by inhalation (such as intranasal spray), intravitreally (such as intravitreal), or buccally. As used herein, the term "parenteral" refers to a mode of administration that includes intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous, intradermal, and intraarticular injections and infusions. Thus, in certain embodiments, the composition is formulated for delivery by any of these routes of administration.

[0341] In certain embodiments, a pharmaceutical composition for parenteral injection includes a pharmaceutically acceptable sterile aqueous or non-aqueous solution, dispersion, suspension, or emulsion, or sterile powder for reconstitution into a sterile injectable solution or dispersion immediately prior to use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.), carboxymethylcellulose and suitable mixtures thereof, β-cyclodextrin, vegetable oils (such as olive oil), and organic esters for injection such as ethyl oleate. Suitable fluidity can be maintained, for example, by the use of coating materials such as lecithin, by maintaining the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents, and dispersing agents. Prolonged absorption of the injectable pharmaceutical form can be brought about by including agents that delay absorption such as aluminum monostearate and gelatin.

[0342] In some embodiments, the compounds of the present disclosure, or pharmaceutical compositions comprising the compounds of the present disclosure, are suspended in a sustained-release matrix. As used herein, a sustained-release matrix is a matrix made of a material that is degradable by enzymatic hydrolysis or acid-base hydrolysis or dissolution, usually a polymer. When inserted into the body, the matrix is acted upon by enzymes and body fluids. The sustained-release matrix is preferably selected from biocompatible materials such as liposomes, polylactide (polylactic acid), polyglycolide (a polymer of glycolic acid), polylactide co-glycolide (a copolymer of lactic acid and glycolic acid), polyanhydrides, poly(ortho)esters, polypeptides, hyaluronic acid, collagen, chondroitin sulfate, carboxylic acids, fatty acids, phospholipids, polysaccharides, nucleic acids, polyamino acids, amino acids such as phenylalanine, tyrosine, isoleucine, polynucleotides, polyvinylpropylene, polyvinylpyrrolidone, and silicone. One embodiment of the biodegradable matrix is a matrix of any of polylactide, polyglycolide, or polylactide co-glycolide (a copolymer of lactic acid and glycolic acid).

[0343] Injectable depot forms include those prepared by forming a microcapsule matrix of a peptide compound in one or more biodegradable polymers such as poly(lactide-co-glycolide), poly(ortho esters), poly(anhydrides), and (poly)glycols such as PEG. Depending on the ratio of the peptide to the polymer and the nature of the particular polymer used, the release rate of the peptide compound can be controlled. Depot injectable formulations can also be prepared by encapsulating the peptide compound in liposomes or microemulsions that are compatible with body tissues.

[0344] Injectable formulations can be sterilized, for example, by filtration through a bacteria-retaining filter or by including a sterilizing agent in the form of a sterile solid composition that can be dissolved or dispersed in sterile water or other sterile injectable medium immediately before use.

[0345] Examples of topical administration include administration to the skin or mucosa such as the surface of the lungs and eyes. Compositions for topical pulmonary administration, including those for inhalation and intranasal use, may include solutions and suspensions of aqueous and non-aqueous formulations, and may be prepared as dry powders that may or may not be compressed. In non-compressed powder compositions, the active ingredient may be in a finely divided form and may be used in admixture with a pharmaceutically acceptable inert carrier of a larger size, for example, including particles having a size of up to 100 micrometers in diameter. Suitable inert carriers include sugars such as lactose.

[0346] Alternatively, the composition may be compressed and may contain a compressed gas such as nitrogen or a liquefied gas propellant. The liquefied propellant medium, and indeed the entire composition, can be made such that the active ingredient does not dissolve therein to a substantial extent. The compressed composition may also contain a surfactant such as a liquid or solid non-ionic surfactant, or may be a solid anionic surfactant. In some embodiments, a solid anionic surfactant in the form of a sodium salt can be used.

[0347] A further form of topical administration is to the eye. The peptide compounds of the present disclosure can be incorporated into a pharmaceutically acceptable ophthalmic vehicle and delivered such that the peptide compound is maintained in contact with the eye surface for a sufficient time to permit penetration of the peptide compound into the cornea and the internal regions of the eye, such as the anterior chamber, posterior chamber, vitreous body, aqueous humor, vitreous humor, cornea, iris / ciliary body, lens, choroid / retina, and sclera. The pharmaceutically acceptable ophthalmic vehicle can be, for example, an ointment, a vegetable oil, or an encapsulating material. Alternatively, the peptide compounds disclosed herein can be directly injected into the vitreous humor and aqueous humor.

[0348] Compositions for rectal or vaginal administration include suppositories prepared by mixing the peptides of the present disclosure with a suitable non-irritating excipient or carrier such as cocoa butter, polyethylene glycol, or suppository wax, which is solid at room temperature but liquid at body temperature and thus melts in the rectal or vaginal cavity to release the active compound.

[0349] The peptide compounds disclosed herein can also be administered by incorporation into liposomes or other lipid-based carriers. As is known in the art, liposomes generally are derived from phospholipids or other lipid substances. Liposomes are formed by single or multiple layers of hydrated liquid crystals dispersed in an aqueous medium. Any non-toxic, physiologically acceptable, metabolizable lipid capable of forming liposomes can be used. The compositions in liposome form can contain, in addition to the peptide compounds disclosed herein, stabilizers, preservatives, excipients, and the like. In certain embodiments, the lipids include phospholipids such as phosphatidylcholine (lecithin) and serine (both natural and synthetic). Methods for forming liposomes are known in the art.

[0350] The pharmaceutical compositions used in the present disclosure suitable for parenteral administration may generally contain a sterile aqueous solution and / or suspension of the peptide compound made isotonic with the recipient's blood using, for example, sodium chloride, glycerin, glucose, mannitol, sorbitol, and the like.

[0351] Oral administration An example of a method of administering the compounds or pharmaceutical compositions thereof disclosed herein is oral administration.

[0352] The present disclosure provides pharmaceutical compositions for oral delivery. The compositions and peptides of the present disclosure can be prepared for oral administration according to any of the methods, techniques, and / or delivery vehicles described herein. Further, one of ordinary skill in the art will understand that the peptides of the present disclosure can be modified or incorporated into systems or delivery vehicles that are not disclosed herein but are well known in the art and suitable for use in the oral delivery of peptides.

[0353] In certain embodiments, formulations for oral administration may include adjuvants (e.g., nonionic surfactants such as resorcinol and / or polyoxyethylene oleyl ether and n-hexadecyl polyethylene ether) for artificially increasing the permeability of the intestinal wall, and / or enzyme inhibitors (e.g., pancreatic trypsin inhibitor, diisopropyl fluorophosphate (DFF) or trasylol) for inhibiting enzymatic degradation. In certain embodiments, peptide compounds in solid dosage forms for oral administration can be mixed with at least one additive such as sucrose, lactose, cellulose, mannitol, trehalose, raffinose, maltitol, dextran, starch, agar, alginate, chitin, chitosan, pectin, tragacanth gum, gum arabic, gelatin, collagen, casein, albumin, synthetic or semi-synthetic polymers, or glycerides.

[0354] These dosage forms can also contain other types of additives, such as inert diluents, lubricants such as magnesium stearate, preservatives such as parabens, sorbic acid, antioxidants such as ascorbic acid, alpha-tocopherol, cysteine, disintegrants, binders, thickeners, buffers, pH adjusters, sweeteners, flavoring agents, or fragrances.

[0355] In some embodiments, an oral dosage form or unit dose suitable for use with the peptide compounds disclosed herein may include a mixture of the peptide compound and a non-drug component or excipient, as well as other non-reusable materials that may be considered components or packaging. The oral composition may include at least one of liquid, solid, and semi-solid dosage forms. In some embodiments, an oral dosage form containing an effective amount of the peptide compound is provided, and the dosage form includes at least one of pills, tablets, capsules, gels, pastes, beverages, syrups, ointments, and suppositories. In some examples, an oral dosage form is provided that is designed and configured to achieve delayed release of the peptide compound in the small intestine and / or colon of a subject.

[0356] In one embodiment, an oral pharmaceutical composition comprising a peptide compound disclosed herein comprises an enteric coating designed to delay the release of the peptide compound in the small intestine. In at least some embodiments, a pharmaceutical composition is provided that comprises a peptide compound disclosed herein and a protease inhibitor such as aprotinin in a sustained release pharmaceutical formulation. In some examples, the pharmaceutical composition of the present disclosure comprises an enteric coat that is soluble in gastric juice at a pH of about 5.0 or greater. In at least one embodiment, a pharmaceutical composition is provided that comprises an enteric coating comprising a polymer having dissociable carboxylic acid groups, such as derivatives of cellulose such as hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and cellulose acetate trimellitate, and similar derivatives of cellulose and other carbohydrate polymers.

[0357] In one embodiment, a pharmaceutical composition comprising a peptide compound disclosed herein is provided in an enteric coating, the enteric coating being designed to protect and release the pharmaceutical composition in a controlled manner within the lower gastrointestinal system of a subject and avoid systemic side effects. In addition to the enteric coating, the peptide compounds of the present disclosure can be encapsulated, coated, incorporated, or otherwise bound within any suitable oral drug delivery system or component. For example, in some embodiments, the peptide compounds disclosed herein are provided in a lipid-based delivery system comprising at least one of a polymeric hydrogel, nanoparticles, microspheres, micelles, and other lipid-based systems.

[0358] To overcome peptide degradation in the small intestine, some embodiments disclosed herein include a hydrogel polymer delivery system comprising a peptide compound disclosed herein, whereby the hydrogel polymer protects the peptide compound from proteolysis in the small intestine and / or colon. The peptide compounds disclosed herein can be further formulated for compatible use with delivery systems designed to enhance dissolution rate and intestinal absorption of the peptide. These methods include the use of liposomes, micelles, and nanoparticles to increase peptide permeation through the GI tract.

[0359] One or more peptide compounds disclosed herein can also be combined with various biological response systems to provide pharmaceuticals for oral delivery. In some embodiments, the peptides of the present disclosure are used in combination with a hydrogel having a hydrogen bonding group and a bioresponsive system such as a mucoadhesive polymer (e.g., PEG, poly(methacrylic) acid [PMAA], cellulose, Eudragit®, chitosan, and alginate) to provide a therapeutic agent for oral administration. Other embodiments are methods of optimizing or extending the drug residence time of the peptide compounds disclosed herein, including methods of modifying the surface of the peptide compound to have mucoadhesiveness via hydrogen bonding, a polymer having bound mucin, and / or hydrophobic interactions. These modified peptide molecules can demonstrate an increase in drug residence time within a subject according to the desired characteristics of the present disclosure. Additionally, a targeted mucoadhesive system can specifically bind to receptors on the surface of enterocytes and M cells, thereby further increasing the uptake of particles containing the peptide compound.

[0360] Permeation enhancer Other embodiments are methods for oral delivery of the peptide compounds disclosed herein, including methods in which the peptide compound is provided to a subject in combination with a permeation enhancer that promotes the transport of the peptide across the intestinal mucosa by increasing paracellular or transcellular permeation. Various permeation enhancers and methods for oral delivery of therapeutic agents are described in Bray den, D.J., Mrsny, R.J., 2011. Oral peptide delivery: prioritizing the leading technologies. Ther. Delivery 2(12), 1567 - 1573.

[0361] In certain embodiments, the pharmaceutical compositions and formulations disclosed herein comprise a peptide compound disclosed herein and one or more absorption enhancers. Examples of absorption enhancers include, for example, bile salts, fatty acids, surfactants (anionic, cationic, and nonionic) chelating agents, Zonular OT, esters, cyclodextrins, dextran sulfate, azone, crown ethers, EDTA, sucrose esters, and phosphatidylcholine. Absorption enhancers are typically not carriers per se, but are widely associated with other carriers to improve oral bioavailability by transporting peptides and proteins across the intestinal mucosa. Such substances can be added to the formulation as excipients or incorporated to form nonspecific interactions with the peptide compound of interest.

[0362] Food components and other naturally occurring substances that have been identified as enhancing tight junction permeability and that are generally recognized as safe (GRAS) include, for example, glycerides, acylcarnitines, bile salts, and medium-chain fatty acids. The sodium salts of medium-chain fatty acids (MCFAs) have also been suggested to be absorption enhancers. The most widely studied MCFA is sodium caprylate, which is the salt of capric acid and contains 2-3% of the fatty acids in the milk fat fraction. To date, sodium caprylate has been mainly used as an excipient in suppository formulations (Doktacillin™) to improve rectal ampicillin absorption. The permeation characteristics of another dietary MCFA, sodium caprylate (8-carbon), have been shown to be lower in vitro compared to sodium caprylate. Sodium caprylate and a peptide drug were formulated by mixing them into a mixture of oil and other excipients to produce an oil-based suspension (OS) with enhanced permeability (Tuvia, S. et al., Pharmaceutical Research, Vol. 31, No. 8, pp. 2010-2021 (2014)).

[0363] For example, in one embodiment, the permeation enhancer is combined with a peptide compound, and the permeation enhancer includes at least one of medium-chain fatty acids, long-chain fatty acids, bile salts, amphiphilic surfactants, and chelating agents. In certain embodiments, medium-chain fatty acid salts promote absorption by increasing the paracellular permeability of the intestinal epithelium. In one embodiment, a permeation enhancer containing sodium N-[hydroxybenzoyl)amino]caprylate is used to form a weak non-covalent association with the peptide of the present disclosure, and the permeation enhancer promotes membrane transport and further dissociation when it reaches the blood circulation. In another embodiment, the peptide compound disclosed herein is bound to oligoarginine, thereby increasing the cellular permeation of the peptide into various cell types. Further, in at least one embodiment, a non-covalent bond is formed between the peptide compound disclosed herein and a permeation enhancer selected from the group consisting of cyclodextrin (CD) and dendrimer, and the permeation enhancer reduces peptide aggregation and increases the stability and solubility of the peptide compound molecules.

[0364] In certain embodiments, the pharmaceutical composition or formulation includes the peptide compound disclosed herein and a transient permeability enhancer (TPE). The permeation enhancer and TPE may be used to increase the oral bioavailability or the peptide compound. An example of a TPE that can be used is an oily suspension formulation that disperses a powder containing sodium caprylate and a therapeutic agent (Tuvia, S. et al., Pharmaceutical Research, Vol. 31, No. 8, pp. 2010 - 2021 (2014)).

[0365] In certain embodiments, the pharmaceutical composition and formulation may include the peptide compound disclosed herein and one or more absorption promoters, enzyme inhibitors, or mucoadhesive polymers.

[0366] In some embodiments, the peptide compound disclosed herein is formulated into a formulation vehicle, such as an emulsion, liposome, microsphere, or nanoparticle.

[0367] Other embodiments disclosed herein provide methods of treating a subject with a peptide compound disclosed herein that has an increased half-life. In one aspect, the disclosure provides a peptide compound that has a half-life in vitro or in vivo (e.g., when administered to a human subject) of at least several hours to one day, sufficient to administer a therapeutically effective amount once daily (q.d.) or twice daily (b.i.d.). In another embodiment, the peptide compound has a half-life of three days or more sufficient to administer a therapeutically effective amount once weekly (q.w.). Further, in another embodiment, the peptide compound has a half-life of eight days or more sufficient for alternate week (B.i.w.) or monthly administration of a therapeutically effective amount. In another embodiment, the peptide compound is derivatized or modified to have a longer half-life compared to an underivatized or unmodified peptide compound. In another embodiment, the peptide compound comprises one or more chemical modifications to increase serum half-life.

[0368] When used in at least one of the treatment or delivery systems described herein, the peptide compounds disclosed herein can be used in pure form or, if such form exists, in pharmaceutically acceptable salt form.

[0369] The total daily usage amount of the peptide compounds and compositions disclosed herein can be determined by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dosage level for any particular subject will depend upon a variety of factors including a) the disorder being treated and the severity of the disorder; b) the activity of the specific compound being used; c) the specific composition being used, the age, weight, general health status, sex and diet of the patient; d) the time of administration, route of administration and rate of excretion of the specific peptide compound being used; e) the duration of the treatment; f) drugs used in combination with or concurrently with the specific peptide compound being used, and similar factors well known in the medical arts.

[0370] Administration The term "therapeutically effective amount" of a compound refers to an amount of the compound that is non-toxic but sufficient to produce the desired effect. The amount of the compound of formula (I) or (Ia) required to achieve the desired biological effect will depend on a number of factors (e.g., the specific compound selected, the intended use, the mode of administration, and the clinical condition of the patient). The appropriate "effective" amount in any individual case can be determined by one of ordinary skill in the art using routine experimentation. For example, a "therapeutically effective amount" of the compound of formula (I) or (Ia) is about 0.01 - 50 mg / dose, or 0.02 - 1 mg / dose, or, for example, 0.0001 - 300 mg / kg body weight per day or 1 - 300 mg / kg body weight per day.

[0371] In the case of parenteral application, it may be preferable for the corresponding formulation to contain at least one antibacterial preservative in order to inhibit the growth of microorganisms and bacteria between administrations.

[0372] Dosage units, packages, pen devices, and administration The compounds disclosed herein can be prepared for use as suitable pharmaceutical compositions. This suitable pharmaceutical composition can be in the form of one or more dosage units.

[0373] This composition can be prepared by any suitable pharmaceutical method including the step of contacting the compound disclosed herein with a carrier which can consist of one or more additional ingredients.

[0374] Dosage units can be, for example, capsules, tablets, dragees, granule sachets, drops, solutions, suspensions, lyophilized products, and powders, each of which contains a defined amount of the compound disclosed herein.

[0375] Each of the above-described dosage units of the compounds disclosed herein or the pharmaceutical compositions (dosage units) disclosed herein can be provided in a package to facilitate transport and storage. Dosage units are contained in standard single-dose or multi-dose packages, the form, material, and shape of which are determined by the type of unit being prepared.

[0376] In some embodiments, the present disclosure provides a kit comprising a compound of any of the stereoisomeric forms of formula (I) or (Ia), or a physiologically acceptable salt or solvate thereof, and a set of instructions for the use of the compound for the methods described herein. In some embodiments, the kit further comprises one or more inert carriers and / or diluents. In some embodiments, the kit further comprises one or more other pharmacologically active compounds (e.g., those described herein).

[0377] In certain embodiments, the dosage unit may be provided with a device for administration, for example, with a syringe, an injection pen, or an autoinjector. Such a device may be provided separately from the pharmaceutical composition or the pharmaceutical composition may be pre-filled.

[0378] A "pen-type injection device" (often simply referred to as an "injection pen") is typically an injection device having an elongated shape similar to a fountain pen. Such pens usually have a tubular cross-section, but can easily have various cross-sections such as triangular, rectangular, or square, or any variation around these geometric shapes. Generally, a pen-type injection device includes the following three main elements: a cartridge section that often houses a cartridge within a housing or holder; a needle assembly connected to one end of the cartridge section; and a dosing section connected to the other end of the cartridge section. The cartridge (often also referred to as an "ampoule") typically includes an upper portion having a reservoir filled with a drug, a movable rubber-type stopper or piston located at one end of the cartridge reservoir, and a penetrable rubber seal located at the other end (often the constricted end). A crimped annular metal band is typically used to hold the rubber seal in place. The cartridge housing can typically be made of plastic, while the cartridge reservoir has historically been made of glass.

[0379] Combination therapy In some embodiments, the methods disclosed herein include administering to a subject in need thereof a peptide compound (i.e., a first therapeutic agent) disclosed herein in combination with a second therapeutic agent. In certain embodiments, the second therapeutic agent is administered to the subject before and / or at the same time as and / or after the peptide compound is administered to the subject. In some embodiments, the second therapeutic agent is an anti-inflammatory agent. In certain embodiments, the second therapeutic agent is a non-steroidal anti-inflammatory drug, a steroid, or an immunomodulatory agent.

[0380] In another embodiment, the method includes administering a third therapeutic agent to the subject. In certain embodiments, the second therapeutic agent is an antibody that binds to IL-23 or IL-23R.

[0381] This combination of active ingredients can be used, in particular, for a synergistic improvement of the action. These can be applied by separate administration of the active ingredients to the patient or in the form of a combined product in which several active ingredients are present in one pharmaceutical preparation. The amounts of the compounds and other pharmaceutically active ingredients disclosed herein, as well as the relative administration times, are selected to achieve the desired combined therapeutic effect. The administration of this combination can be simultaneous in (1) a single pharmaceutical composition containing all pharmaceutically active ingredients; or (2) separate pharmaceutical compositions, each containing at least one of the pharmaceutically active ingredients. Alternatively, this combination can be administered separately in a sequential manner in which one therapeutic agent is administered first and the other therapeutic agent is administered second or vice versa. When the active ingredients are administered by separate administration of these active ingredients, this can be done simultaneously or sequentially.

[0382] Other active substances suitable for such combinations include, for example, those that enhance the therapeutic effect of one or more active substances with respect to one of the stated indications and / or those that make it possible to reduce the dosage of one or more active substances.

[0383] In another aspect, the present disclosure relates to the use of a compound according to the present disclosure or a physiologically acceptable salt thereof, in combination with at least one of the above-described active substances as a combination partner, for preparing a pharmaceutical suitable for treating or preventing a disease or condition that may be affected by binding to receptor interleukin-23 and modulating its activity. This includes, for example, diseases related to the immune system, such as one of the diseases or conditions listed above, for example, irritable bowel syndrome, Crohn's disease, psoriasis, and ulcerative colitis, or complications thereof.

[0384] The use of a compound according to the present disclosure or a physiologically acceptable salt thereof in combination with one or more active substances can be carried out simultaneously, separately, or sequentially.

[0385] The use of a compound according to the present disclosure or a physiologically acceptable salt thereof in combination with another active substance can be carried out simultaneously or with a time lag, for example, within a short period. When administering these simultaneously, the two active substances are administered to the patient together.

[0386] As a result, in another aspect, the present disclosure relates to a pharmaceutical comprising a compound according to the present disclosure or a physiologically acceptable salt of such a compound, and at least one of the above-described active substances as a combination partner, optionally together with one or more inert carriers and / or diluents.

[0387] The compound according to the present disclosure or a physiologically acceptable salt or solvate thereof, and the additional active substance combined therewith, may both be present together in one formulation (for example, a tablet, capsule, or solution), or separately in two identical or different formulations (for example, a so-called kit of parts).

[0388] Another subject matter disclosed herein is a process for preparing a compound of formula (I) or (Ia), as well as salts and solvates thereof, by which this compound can be obtained, and this preparation process is exemplified below.

Examples

[0389] Method The abbreviations used are as follows. AA Amino acid ACN Acetonitrile Aib α-Amino-isobutyric acid Boc tert-Butyloxycarbonyl tBu Tert-butyl CV Column volume DCM Dichloromethane DIC N,N’-Diisopropylcarbodiimide DIPEA N,N-Diisopropylethylamine DMF Dimethylformamide DODT 3,6-Dioxa-1,8-octanedithiol DPBS Dulbecco's phosphate buffered saline EDC 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide EDT Ethanedithiol Fmoc Fluorenylmethyloxycarbonyl g Gram HATU O-(7-Azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate HBTU 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium hexafluorophosphate HOAt 1-Hydroxy-7-azabenzotriazole HOBt 1-Hydroxybenzotriazole HPLC High performance liquid chromatography LC / MS Liquid chromatography / mass spectrometry mM Millimolar concentration Mmt Monomethoxy-trityl n.a. Not applicable n.d. Undetermined nM Nanomolar concentration PBS Phosphate buffered saline Pfp 2,2,4,6,7 - pentamethyldihydrobenzofuran - 5 - sulfonyl PyBOP Benzotriazol - 1 - yloxytris(pyrrolidino)phosphonium hexafluorophosphate tBu tert - butyl TFA Trifluoroacetic acid Trt Trityl / triphenylmethyl TSTU N,N,N’,N’ - tetramethyl - O - (N - succinimidyl)uronium tetrafluoroborate UPLC Ultra - performance liquid chromatography UV Ultraviolet

[0390] Materials Various Rink - Amide resins (e.g., 4 - (2’,4’ - dimethoxyphenyl - Fmoc - aminomethyl)-phenoxyacetamido - norleucylmethyl resin, Merck Biosciences; 4 - [(2,4 - dimethoxyphenyl)(Fmoc - amino)methyl]phenoxyacetamidomethyl resin, Agilent Technologies) were used for the synthesis of peptide amides at a loading in the range of 0.2 - 0.7 mmol / g.

[0391] Fmoc-protected natural amino acids were purchased from Protein Technologies Inc, Senn Chemicals, Merck Biosciences, Novabiochem, Iris Biotech, Bachem, Chem-Impex International, or MATRIX Innovation. Throughout the synthesis, the following standard amino acids were used: Fmoc-L-Ala-OH, Fmoc-Arg(Pbf)-OH, Fmoc-L-Asn(Trt)-OH, Fmoc-L-Asp(OtBu)-OH, OH, Fmoc-L-Gln(Trt)-OH, Fmoc-L-Glu(OtBu)-OH, Fmoc-L-Leu-OH, Fmoc-L-Lys(Boc)-OH, Fmoc-D-Lys(Boc)-OH, Fmoc-L-Phe-OH, Fmoc-L-Thr(tBu)-OH, Fmoc-L-Trp(Boc)-OH, Fmoc-L-Tyr(tBu)-OH, Fmoc-Cys(Trt)-OH.

[0392] In addition, the following special amino acids were purchased from the same supplier as above. Fmoc-L-1-Nal-OH, Fmoc-L-2-Nal-OH, Fmoc-L-Phe(2-Ae-Boc)-OH (Fmoc-L-Yae(Boc)-OH), Fmoc-L-Phe(Me)-OH (Fmoc-L-Yme-OH), Fmoc-Yde-OH, Fmoc-L-Orn(Boc), Fmoc-L-Trp(Me)-OH, Fmoc-L-Agb(Pbf)-OH, Fmoc-Ahx-OH, Fmoc-Aoa-OH, Fmoc-Apt-OH, Fmoc-Bal-OH, Fmoc-Hme-OH, Fmoc-Kme(Boc)-OH, Fmoc-L-Lys(Ac)-OH, e-Fmoc-L-Lys(aAc)-OH, Fmoc-Mkdm-OH, Fmoc-Mle-OH, Fmoc-Mep-OH, Fmoc-Mly(Boc)-OH, e-Fmoc-Ndmk-OH, Fmoc-Nmapt-OH, Fmoc-Nmc(Trt)-OH, Fmoc-Nmd(O-tBu)-OH, Fmoc-Nme(O-tBu)-OH, Fmoc-Nmha-OH, Fmoc-Nmn(Trt)-OH, Fmoc-Pal-OH, Fmoc-Pen(Trt)-OH, Fmoc-Pyal-OH, Fmoc-Sar-OH and Fmoc-Thp-OH.

[0393] Furthermore, dicarboxylic acid Dad was purchased and used from the same supplier as mentioned for the amino acids in the form of di-N-hydroxysuccinimide ester, i.e., Dad(Di-O-Succ).

[0394] Synthesis of Mkdm 470 mg of (2S)-6-(tert-butoxycarbonylamino)-2-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoic acid was treated with 5 mL of TFA for 2 hours. Then, 100 mL of water was added and the solution was lyophilized. The residue was dissolved in 10 mL of methanol. Subsequently, 129 mg of DIPEA, 126 mg of NaCNBH3 and 50 mg of formaldehyde were added and the mixture was stirred for 1 hour. The product was purified by chromatography to obtain a yield of 230 mg.

[0395] Analysis of UPLC / UV / MS method Method A: Detection at 214 nm HPLC: Waters i-Class UPLC Column: Waters ACQUITY UPLC (R) CSH (TM) C18 1.7 μm (75×2.1 mm), 50 °C Solvent: H2O + 0.05% TFA: ACN + 0.045% TFA (flow rate 0.7 ml / min) Gradient: 95:5 (0 min) ~ 95:5 (1 min) ~ 20:80 (12 min) ~ 5:95 (12.5 min) ~ 5:95 (13.5 min) ~ 95:5 (14 min) ~ 95:5 (16 min) Mass spectrometer: Waters Xevo G2-XS QTof, electrospray positive ion mode, mass range: 300 - 3200 m / z, resolution mode is used

[0396] Method B: Detection at 214 nm HPLC: Agilent 1290 Infinity II UPLC Column: Waters ACQUITY UPLC (R) CSH (TM) C18 1.7 μm (150×2.1 mm), 50 °C Solvent: H2O + 0.05% TFA: ACN + 0.035% TFA (flow rate 0.5 ml / min) Gradient: 80:20 (0 min) ~ 80:20 (3 min) ~ 25:75 (23 min) ~ 2:98 (23.5 min) ~ 2:98 (30.5 min) ~ 80:20 (31 min) ~ 80:20 (37 min) Mass spectrometer: Agilent 6230 Accurate-Mass TOF, Agilent Dual Jet Stream ESI+, mass range: 300 - 3200 m / z, extended dynamic range mode (2Ghz) is used

[0397] Method C: Detection at 214 nm HPLC: Agilent 1290 Infinity II UPLC Column: Waters ACQUITY UPLC® CSH™ C18 1.7 μm (150×2.1 mm), 50 °C Solvent: H2O + 0.05% TFA: ACN + 0.035% TFA (flow rate 0.5 ml / min) Gradient: 95:5 (0 min) ~ 95:5 (3 min) ~ 40:60 (23 min) ~ 2:98 (23.5 min) ~ 2:98 (30.5 min) ~ 95:5 (31 min) ~ 95:5 (37 min) Mass analyzer: Agilent 6230 Accurate-Mass TOF, Agilent Dual Jet Stream ESI, Mass range: 300~3200 m / z, using Extended Dynamic Range mode (2 Ghz)

[0398] Method D: Detection at 220 nm HPLC: Shimadzu Nexera X2 Column: Waters ACQUITY UPLC® BEH™ C18 1.7 μm (100×2.1 mm), 40 °C Solvent: H2O + 0.1% TFA: ACN + 0.1% TFA (flow rate 0.5 ml / min) Gradient: 95:5 (0 min) ~ 95:5 (3 min) ~ 40:60 (23 min) ~ 2:98 (23.5 min) ~ 2:98 (30.5 min) ~ 95:5 (31 min) ~ 95:5 (37 min) Mass analyzer: LCMS 2020, DL-temperature: 250 °C, Spray gas flow: 1.5 L / min, Detector voltage: 1.4 KV

[0399] Method E: Detection at 214 nm HPLC: Agilent 1290 Infinity II UPLC Column: Waters ACQUITY UPLC® CSH™ C18 1.7 μm (150×2.1 mm), 50 °C Solvent: H2O + 0.05% TFA: ACN + 0.035% TFA (flow rate 0.5 ml / min) Gradient: 99:1 (0 min) ~ 99:1 (3 min) ~ 70:30 (18 min) ~ 2:98 (18.5 min) ~ 2:98 (25.5 min) ~ 99:1 (26 min) ~ 99:1 (32 min) Mass analyzer: Agilent 6230 Accurate-Mass TOF, Agilent Dual Jet Stream ESI, mass range: 300 - 3200 m / z, using Extended Dynamic Range mode (2Ghz)

[0400] Method F: Detection at 214 nm HPLC: Agilent 1290 Infinity II UPLC Column: Waters ACQUITY UPLC® CSH™ C18 1.7 μm (150×2.1 mm), 50 °C Solvent: H2O + 0.05% TFA: ACN + 0.045% TFA (flow rate 0.5 ml / min) Gradient: 95:5 (0 min) ~ 95:5 (3 min) ~ 80:20 (25 min) ~ 2:98 (25.5 min) ~ 2:98 (30.5 min) ~ 95:5 (31 min) ~ 95:5 (35 min) Mass analyzer: Agilent 6230 Accurate-Mass TOF, Agilent Dual Jet Stream ESI, mass range: 300 - 3200 m / z, using Extended Dynamic Range mode (2Ghz)

[0401] Method G: Detection at 214 nm HPLC: Agilent 1290 Infinity II UPLC Column: Waters ACQUITY UPLC® CSH™ C18 1.7 μm (150×2.1 mm), 50 °C Solvent: H2O + 0.05% TFA: ACN + 0.045% TFA (flow rate 0.5 ml / min) Gradient: 95:5 (0 min) ~ 95:5 (3 min) ~ 80:20 (30 min) ~ 2:98 (30.5 min) ~ 2:98 (34.5 min) ~ 95:5 (35 min) ~ 95:5 (40 min) Mass analyzer: Agilent 6230 Accurate-Mass TOF, Agilent Dual Jet Stream ESI, mass range: 300 - 3200 m / z, using Extended Dynamic Range mode (2Ghz)

[0402] General preliminary HPLC purification procedure The crude peptide compound was purified using an Aekta Purifier System, a Jasco semiprep HPLC System, a Waters Autopurification System, an Agilent 1100 HPLC system or a similar HPLC system. Depending on the amount of the crude peptide to be purified, preparative RP-C18-HPLC columns with different sizes and flow rates were used. For example, the following columns were used: Waters XSelect CSH C18 OBD Prep 5μm 30×250mm, Waters SunFire C18 OBD Prep 5μm 30×250mm, Waters SunFire C18 OBD Prep 5μm 50×150mm, and Phenomenex Luna Prep C18 5μm 21.2×250mm. As the eluent, acetonitrile (B), and water + 0.1% TFA (A) or water + 0.1% TFA (A) were used. The product-containing fractions were collected and lyophilized to obtain the purified product typically as the TFA salt.

[0403] Alternatively, the peptide compound can be isolated as an acetate salt by the following procedure. The peptide compound was dissolved in water and the solution was adjusted to pH 7.05 with NaHCO3. Then, the dissolved compound was purified using RP Kinetex 21, 2×250mm (Column Volume CV 88ml, 5μm, C18, 100A, Aekta avant 25). The column was equilibrated with solvent A (3×CV), the compound was injected, and then washed with a mixture of solvent A (95%) and solvent B (5%) at 3CV. Then, a gradient of solvent A:B (95:5) to A:B (20:80) was run at 15CV. The purified peptide was collected and lyophilized.

[0404] General synthesis of peptide compounds Solid-phase peptide synthesis Solid-phase peptide synthesis was carried out using standard Fmoc chemistry and HBTU / DIPEA or HATU / DIPEA activation on a Prelude Peptide Synthesizer (Protein Technologies), or a similar automated synthesizer. DMF was used as the solvent.

[0405] Deprotection: 20% piperidine / DMF for 2.5 minutes twice Washing: 7 times with DMF Coupling: Twice for 20 minutes with 2M DIPEA in 500mM HBTU / NMP in 200mM AA / DMF at 5 / 5 / 13. Washing: 5 times with DMF.

[0406] HBTU / DIPEA activation was used for all standard couplings.

[0407] For N-terminal acetylated peptides, the N-terminal Fmoc protecting group was removed and the peptide was treated twice for 20 minutes with a 10% solution of acetic anhydride and DIPEA with shaking.

[0408] The peptide was cleaved from the resin with King's cleavage cocktail consisting of 82.5% TFA, 5% phenol, 5% water, 5% thioanisole, and 2.5% EDT, or with a modified cleavage cocktail consisting of 82.5% TFA, 5% phenol, 5% water, 5% thioanisole, and 2.5% DODT. The crude peptide was then precipitated with diethyl or diisopropyl ether, centrifuged, and lyophilized. The peptide was analyzed by analytical HPLC and checked by ESI mass spectrometry. The crude peptide was purified by conventional preparative RP-HPLC purification procedures as described in the HPLC section.

[0409] Peptide synthesis of PyEA at position X13 For PyEA at position X13, Wang resin was used. Following construction of the sequence on the resin, cleavage of the peptide from the resin and subsequent cyclization, solid-phase synthesis was initiated from the C-terminal attachment of the X12 amino acid to the resin.

[0410] The free C-terminal carboxylic acid of the peptide was treated with TSTU (1 eq) and DIPEA (2 eq) in DMF for 1 hour. Then, PyEA (1 eq) was added to the solution to obtain the desired product. The mixture was purified by chromatography as described in the UPLC section.

[0411] Peptide synthesis using dicarboxylic acid (Dad) at the X1 position The purified peptide was dissolved in DMF. 10 eq of DiPEA was added, then 0.95 eq of di-OSu-ester in DMF was added dropwise and the mixture was stirred at room temperature for 5 minutes. Then, the mixture was purified by chromatography.

[0412] Synthesis of the peptide according to formula (Ia) Synthesis of compound SEQ ID NO: 67 Synthesis of Fmoc-Mly-Palm-OH

Chemical formula

[0413] This amino acid derivative was used at the X10 position in the same manner as a normal amino acid in SPPS, and a peptide was obtained as described in the general SPPS synthesis method.

[0414] Synthesis of compound SEQ ID NO: 71 The synthesis of Sema is described in WO 2011 / 080102 pamphlet which is incorporated by reference.

[0415] For the Sema side chain, Fmoc-protected lysine (1 equivalent) and 1000 mg (1 equivalent) of tert-butyl 18-oxo-18-[[rac-(1S)-1-tert-butoxycarbonyl-4-[2-[2-[2-[2-[2-[2-(2,5-dioxopyrrolidin-1-yl)oxy-2-oxo-ethoxy]ethoxy]ethoxy]ethylamino]-2-oxo-ethoxy]ethoxy]ethylamino]-4-oxo-butyl]amino]octadecenoate (i.e., succinimidyl ester-activated 8-oxo-18-[[(1S)-1-carboxy-4-[2-[2-[2-[2-[2-(carboxymethoxy)ethoxy]ethoxy]ethylamino]-2-oxo-ethoxy]ethoxy]ethylamino]-4-oxo-butyl]amino]octadecanoic acid, where the glutamic acid carboxy group and the terminal carboxy group are protected as tert-butyl esters) was treated with TSTU (1.5 equivalents) and DIPEA (4 equivalents) in DMF (30 mL) and stirred for 15 minutes. The solution was concentrated in vacuo, water (100 mL) was added, and it was lyophilized.

[0416] This derivatized amino acid was used in SPPS. Cysteines at positions X2 and X7 were used in the form of Fmoc-Cys(MMT)-OH. The resin was flushed with dichloromethane and then treated with an iodine solution (5 equivalents) (16 mg / mL) in methanol. The iodine residue was removed with ascorbic acid after 30 minutes to obtain the oxidation product. After flushing with dichloromethane (100 mL), the resin was swollen with DMF (50 mL), and the Fmoc protecting group was cleaved by adding piperidine (8 equivalents, 40 mL) over 10 minutes. This procedure was repeated once.

[0417] Next, 100 mL of Kings Cocktail (85 mL TFA / 5.355 g phenol / 5 mL H2O / 5 mL thioanisole / 2.5 mL ethanedithiol) was used to cleave the peptide (0.1 mmol) from the resin over 3 hours at room temperature. The dissolved peptide was poured into cold ether (700 mL). The precipitated peptide was centrifuged and washed with ether (800 mL). The suspension was filtered, and the solid peptide was dried in vacuo for 1 hour. The peptide was then dissolved in 600 mL of water / acetic acid 99 / 1 (for 1 hour) and lyophilized. The residue was purified by preparative HPLC.

[0418] 30 mg of the dried peptide was dissolved in 10 mL of DMF, and 10 equivalents of diisopropylethylamine were added. 0.95 equivalents of disuccinimidyl succinate were added, and the solution was stirred at room temperature for 1 hour. The solution was concentrated and purified by preparative HPLC to afford the desired product (16 mg).

[0419] Peptide Cyclization Disulfide Cyclization For peptides having two sulfhydryl moieties, the compound was suspended in acetonitrile / water (2 mg / mL) (partially dissolved), and the mixture was treated dropwise with a solution of acetic acid / iodine (5 mL / 80 mg) until the solution turned bright yellow. Ascorbic acid (1.7 g in 100 mL of water) was then added until the yellow color disappeared.

[0420] The solution was diluted with water and lyophilized. The crude peptide was purified by a conventional preparative RP-HPLC purification procedure as described in the HPLC method section. The fractions containing the pure product were then lyophilized in a lyophilizer.

[0421] Lactam Cyclization Subsequent peptide cyclization was carried out under an argon atmosphere. The peptide was dissolved in DMF, then 10 equivalents of DIPEA, 3 equivalents of HOAT and 2 equivalents of EDC were added, and the reaction mixture was stirred at room temperature overnight.

[0422] A peptide containing free thiol (e.g., cysteine, homocysteine (hCys)) and homoserine (OTBDMS) was constructed on Rink Amide - MBHA resin according to the general Fmoc - SPPS procedure.

[0423] Cyclization by thioether formation (X2 is Abu and X7 is Cys) Protected cysteine was used for the formation of thioether monomethoxytrityl (Mmt). The MMT group was cleaved by using 2% TFA (DCM) and 0.5% TIPS in dichloromethane for 15 minutes. This procedure was repeated twice. The resin was washed three times with DCM. Chlorination was carried out at room temperature for 4 hours using dichlorotriphenylphosphorane (6 equivalents) together with pinene (6 equivalents) and thioanisole (4 equivalents) as scavengers. The peptide was cleaved from the resin by treatment with the cleavage reagent 90% trifluoroacetic acid, 5% water, 2.5% 1,2 - ethanedithiol, 2.5% triisopropylsilane. The cleaved peptide was precipitated in cold diethyl ether and then washed twice with ethyl ether. The filtrate was poured off and a second aliquot of cold ether was added and the procedure was repeated. The crude peptide was dissolved in a solution of acetonitrile: water (7:3 containing 1% TFA), filtered to obtain the desired non - cyclized crude peptide. The crude peptide having free thiol (e.g., Cys, hCys, (D)Cys or (D)hCys) and alkyl halide (hSer(Cl)) at either the X2 and X7 positions or the X7 and X2 positions was dissolved in 0.1M TRIS buffer (pH 8.5). Cyclization was carried out overnight at room temperature. Then, the solvent mixture was first diluted 2 - fold with water and then purified by filling into a reverse - phase HPLC apparatus, and then the fractions containing the pure product were lyophilized in a lyophilizer.

[0424] Lactam cyclization Alternatively, the peptide was dissolved in DMF, cooled to 0 °C, and then 20 equivalents of NaHCO3, 3 equivalents of HOAT, and 2.5 equivalents of EDC·HCl were added. The reaction mixture was stirred and allowed to equilibrate slowly overnight at room temperature. NaHCO3 was filtered off by gravity, and the soluble fraction was dried under rotary evaporation. The crude cyclic peptide was dissolved in ACN:water and lyophilized. The desired cyclic peptide product was isolated by conventional preparative RP-HPLC purification procedures.

[0425] In the case of Yae in the sequence, after cleavage from the resin using King's cleavage cocktail and, if applicable, after disulfide ring closure under the above conditions, the N-terminus was left protected with Fmoc, and the deprotected Yae moiety was protected with BOC-OSu (2 equivalents) and diisopropyl-ethylamine in DMF. Subsequently, the N-terminal Fmoc group was cleaved with piperidine (20 equivalents). After workup and purification by RP-HPLC, peptide cyclization was carried out. Finally, the BOC protecting group was cleaved with TFA (50 equivalents). The desired cyclic peptide product was isolated by conventional preparative RP-HPLC purification procedures.

[0426] Cyclization with butanediol or 4-oxo-butyric acid (X1 is Buty or Butyl) After cleavage from the resin and purification by HPLC, the lyophilized peptide was dissolved in methanol. Sodium cyanoborohydride (1 equivalent) and DIPEA (1 equivalent) were added, and the mixture was stirred for 16 h. In the case of butanediol, 1 equivalent was added together with DIPEA. The solvent was evaporated, and the residue was purified by HPLC and lyophilized to give the desired peptide.

[0427] Peptides having Pen as X2 and Pen or Cys as X7 The following peptide compounds in which Cys at the X2 position, or at the X2 and X7 positions, is replaced by Pen (Pen peptide compounds) were prepared as described for the compounds of the present disclosure.

[0428] [Table 34]

[0429] (@) indicates the formation of an ester, thiometer, or disulfide bridge between amino acid residues.

[0430] (§) indicates the formation of a lactam bridge between amino acid residues.

[0431] By these methods, compounds of SEQ ID NOs: 1-74, 101-106, 115, 116, 122, 126, 127, and 149-158 can be obtained, and compounds of SEQ ID NOs: 75-101, 107-121, 123-125, 127-148 can also be obtained. Representative structures are shown in Table 5.

[0432] [Table 35]

[0433] [Table 36]

[0434] [Table 37]

[0435] [Table 38]

[0436] [Table 39]

[0437] [Table 40]

[0438] [Table 41]

[0439] Solubility test of peptides at different pH values Before measuring the solubility of the synthesized peptide batch, its purity was determined by UPLC / MS (Methods B - G).

[0440] For the solubility test, the target concentration was 1 mg pure compound / ml. Therefore, a solution from the solid sample was prepared in a buffer system at a concentration of 1 mg / mL compound. The solid sample was obtained by drying an aliquot of the dimethyl sulfoxide stock solution using a Thermo Speedvac vacuum centrifuge. The drying time was 3 hours.

[0441] Solubility buffer system A) 50 mM HCl pH 1.2 Solubility buffer system B) 50 mM phosphate buffer pH 6.5 Solubility buffer system C) 50 mM phosphate buffer pH 7.4 Solubility buffer system D) 50 mM phosphate buffer pH 9.0

[0442] After gently stirring for 2 hours from the filtered (0.45 μm filter plate) solution, UPLC - UV (Method A) was performed, which was obtained by forced filtration by centrifugation at 1500 RCF for 10 minutes (relative centrifugal acceleration).

[0443] The solubility was determined by comparing the UV peak area of a 2 μL injection of the buffer sample diluted 1:5 with the standard curve of a dimethyl sulfoxide reference sample diluted with dimethyl sulfoxide of known concentration. Different extinction coefficients were considered in the calculation.

[0444] The results are shown in Table 7.

[0445]

Table 42

[0446]

Table 43

[0447]

Table 44

[0448] Evaluation of the Chemical Stability of Peptides Before measuring the chemical stability, the purity of the peptide batch was determined by UPLC / MS (Methods B - G). The target concentration was a pure compound at 1 mg / ml. Solutions from solid samples were prepared in the following buffer systems with a compound concentration of 1 mg / ml based on the previously determined purity %.

[0449] Solubility buffer system A) 50 mM HCl pH 1.2 + acetonitrile (1:1) Solubility buffer system B) 50 mM phosphate buffer pH 6.5 + acetonitrile (1:1) Solubility buffer system C) 50 mM phosphate buffer pH 7.4 + acetonitrile (1:1)

[0450] The prepared solutions were stored at 2 °C and 37 °C for 24 hours. After this time, the samples were centrifuged at 2500 RCF for 15 minutes, and a 1:5 dilution of the supernatant was made. Then, 2 μl of the dilution was analyzed by UHPLC - UV.

[0451] The chemical stability was evaluated by the relative purity loss calculated by the formula: [(Purity after 0 hours at 37 °C) - (Purity after 24 hours at 37 °C)] / (Purity after 0 hours at 37 °C)] × 100% evaluated by the relative purity loss calculated by the formula:

[0452] The purity was calculated as [(Peak area of peptide) / (Total peak area)] × 100%.

[0453] The results are shown in Table 8.

[0454]

Table 45

[0455] Protein stability evaluation of peptides To evaluate the gastric stability of the peptide compounds disclosed herein, tests were conducted in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF).

[0456] For clarity, the term "pepsin - SGF" refers to a solution of simulated gastric fluid containing pepsin, and "SGF medium" refers to a solution of simulated gastric fluid without pepsin. Pepsin - SGF was prepared by dissolving 320 mg of pepsin (Merck Millipore) in 100 mL of SGF medium concentrate (ProSense).

[0457] Similarly, the term "pancreatin - SIF" refers to a solution of simulated intestinal fluid containing pancreatin, and "SIF medium" refers to a solution of simulated intestinal fluid without pancreatin.

[0458] Pancreatin - SIF was prepared by dissolving 1 mg of pancreatin (MP Biomedicals) in 10 mL of SIF medium concentrate (ProSense).

[0459] The peptide was first dissolved in 0.01 HCl (+ / - 10% DMSO) at a stock concentration of 1 mM and further diluted with water to a stock concentration of 20 μM. The final peptide concentration during incubation was 1 μM.

[0460] To 76 μL of pepsin - SGF buffer, 4 μL of 20 μM peptide stock solution was added and incubated at 37 °C. At each time point (0, 60, 120, and 240 minutes), 80 μL of ethanol (0.1% HCOOH) was added to quench the reaction. The samples were centrifuged for 20 minutes, and a 100 μL aliquot of the supernatant was transferred to a LoBind - MTP plate and analyzed by LCMS / MS. The peak area response was calculated for each test compound at each time point. As an internal reference, the peak area response of the same test compound at T0 was calculated. The residual rate at each time point was calculated based on the ratio of the peak area response of the test compound at T0. Time 0 was set to 100%, and all subsequent time points were calculated relative to time 0.

[0461] To 76 μL of pepsin-SGF buffer, 4 μL of 20 μM peptide stock solution was added and incubated at 37 °C. At each time point (0, 60, 120, and 240 minutes), 80 μL of ethanol (0.1% HCOOH) was added to quench the reaction. The samples were centrifuged for 20 minutes, and a 100 μL aliquot of the supernatant was transferred to a LoBind-MTP plate and analyzed by LCMS / MS. The peak area response was calculated for each test compound at each time point. As an internal reference, the peak area response of the same test compound at T0 was calculated. The residual rate at each time point was calculated based on the peak area response ratio of the test compound at T0. Time 0 was set to 100%, and all subsequent time points were calculated relative to time 0.

[0462]

Table 46

[0463]

Table 47

[0464]

Table 48

[0465] Assay of specific human IL23R antibodies The antagonistic effect of the compound against the human interleukin-23 receptor antagonist was examined by ELISA assay.

[0466] The 384-well plates were coated with 50 μl / well of human IL23 at a final concentration of 1 μg / ml and incubated overnight at 4°C. The wells were washed three times with 80 μl of wash buffer, blocked with 80 μl of blocking buffer for 60 minutes at room temperature, and washed again. 20 μl of serially diluted test peptides were added to each well, followed by the addition of 20 μl of recombinant human IL-23R-Fc chimera at a final concentration of 0.1 μg / ml. The plates were incubated for 60 minutes at room temperature. After washing the wells, the bound IL23R-Fc was detected with goat anti-hu-IgG1-HRP antibody. The signal was visualized using QuantaBlu fluorescent peroxidase substrate.

[0467] Assay for the selectivity of specific IL23R antibodies For the selectivity of IL23R antagonist peptides that bind to human IL12Rβ1, recombinant human IL-12Rβ1-Fc was used in an ELISA assay.

[0468] For the selectivity of IL23R antagonist peptides that bind to mouse IL23R, recombinant mouse IL-23R-Fc chimera was used and the bound mouse IL23R-FC was detected using goat anti-mouse IgG1-HRP antibody.

[0469] IL-23-induced STAT3 signaling in HEKBLUE™ IL23 cells HEK-Blue™ IL-23 cells (Invivogen) are designed to detect bioactive human (hIL-23) and mouse IL-23 (mIL-23) by monitoring the activation of the STAT3 pathway. Binding of IL-23 to its receptor on the surface of HEK-Blue™ IL-23 cells triggers a signaling cascade that results in the activation of STAT3 and subsequent production of secreted embryonic alkaline phosphatase (SEAP). This can be readily evaluated using the QUANTI-Blue™ solution, a SEAP detection reagent.

[0470] HEK-Blue™ IL-23 cells were cultured as described by Invivogen.

[0471] On the first day of the assay, 10 μL of HEK-Blue IL23 cell suspension (final concentration: 10,000 cells / well) and 10 μL of serially diluted peptide solution were dispensed into a 384-well assay plate. After pre-incubating the reaction mixture at 37 °C / 5% CO2 / 95% humidity for 60 minutes, 10 μL of human IL23 cytokine (final concentration: 0.25 ng / ml) was added to each well for STAT3 signaling activation. The plate was incubated overnight at 37 °C / 5% CO2 / 95% humidity.

[0472] On the second day, 20 μL / well of Quanti-Blue detection solution (prepared according to the product manual) was dispensed into a new 384-well plate, and then 5 μL of the supernatant of the cell / sample mixture incubated overnight was transferred. After incubating at room temperature for 45 minutes, the signal was measured at OD 620 - 655 nm using PHERAstar (BMG). The dose-response data was fitted with XLfit.

[0473]

Table 49

[0474]

Table 50

[0475]

Table 51

[0476]

Table 52

[0477] As shown in Table 11, the peptide compounds of the present disclosure have a lower ELISA IC 50 for inhibiting the binding of IL23 to its receptor compared to the Pen peptide compounds, demonstrating higher potency.

[0478] [Items of Disclosure] The present disclosure is further characterized by the following items.

[0479] Item 1: Formula (I): [Chemical formula] A compound of wherein - X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad, and Dap, and is bonded to X11 via an amide bond, or alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond. - R1 is absent, or when X1 is selected from the residues of Ahx, Aoa, Apt, Lys, Dab, and Dap, R1 is H, C1 - C4 - alkyl, or acetyl, and is bonded to the amino functional group of X1. - X2 is a residue of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr, and Abu, and an amino acid residue selected from their corresponding d - types. In some embodiments, X2 is a residue of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, and Thr, and an amino acid residue selected from their corresponding d - types. - X7 is a residue of Cys, Glu, Asp, Thr, and Abu, and an amino acid residue selected from their corresponding d - types. X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond, or an ester bond. -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk, and Lys(αAc), -X4 is absent or is an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm, and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp, and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde, and Yae. In some embodiments, X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, and Yde, -X9 is an amino acid residue selected from the residues of Nal, Nak, and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm, and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys, and Orn, and is bonded to X1 via an amide bond, -X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser, and Ala, -X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, PyAl, PyEA, His, Hme, Val, and their corresponding d-forms, -X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy, and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH or -N(C2H5)2, A compound in which the amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, or a salt or solvate thereof, a compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0480] Item 2: X2 is an amino acid residue selected from Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and the amino acid residues corresponding to their d-forms, and X8 is an amino acid residue selected from the amino acid residues of Yme, Tyr, Trp and Yde, or an amino acid residue selected from Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and the amino acid residues corresponding to their d-forms, and X8 is an amino acid residue selected from the amino acid residues of Yme, Tyr, TrP, Yde and Yae, which is any one of the compounds described in Item 1.

[0481] Item 3: The compound according to Item 1, wherein when X2 is Abu or its corresponding d-form, X8 is not an amino acid residue of Yae.

[0482] Item 4: The compound according to Item 1, wherein when X8 is Yae, X2 is not an amino acid residue of Abu or its corresponding d-form.

[0483] Item 5: A compound of formula (I), wherein -X1 is a residue of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad or Dap, and is bonded to X11 via an amide bond, Alternatively, X1 is a residue of Buty or Butyl, which is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond. -R1 is absent or When X1 is a residue of Ahx, Aoa, Apt, Lys, Dab or Dap, R1 is H, C1-C4-alkyl or acetyl, which is bonded to the amino functional group of X1. -X2 is an amino acid residue of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr or Abu, and their corresponding d-forms. -X7 is an amino acid residue of Cys, Glu, Asp, Thr or Abu, and their corresponding d-forms. X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond. -X3 is an amino acid residue of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk or Lys(αAc). -X4 is absent or is an amino acid residue of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp or Thr. -X5 is an amino acid residue of Trp, Wme, Nak, Wcl, Wim, Wdm or Wfl. -X6 is an amino acid residue of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp or Phe. -X8 is an amino acid residue of Yme, Tyr, Trp or Yde. -X9 is an amino acid residue of Nal, Nak or Trp. -X10 is an amino acid residue of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm or Thp. -X11 is an amino acid residue of Asp, Bal, Gab, Glu, Kme, Lys or Orn, and is bonded to X1 via an amide bond, -X12 is absent or is an amino acid residue of Asn, Gly, Ser or Ala, -X13 is absent or is an amino acid residue of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme or Val, and their corresponding d-forms, -X14 is absent or is an amino acid residue of Mep, Sar, Bal, Ile, Dnmy or Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH or -N(C2H5)2, The amide bonds between X1 and X2, X2 and X3, X3 and X4, X4 and X5, and X11 and X1 are optionally methylated, or a salt or solvate thereof, A compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0484] Item 6: -X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, and is bonded to X11 via an amide bond, or X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is absent or When X1 is a residue selected from the residues of Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl, and is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr, and Abu, -X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr, and Abu, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond, or an ester bond, -X3 is an amino acid residue selected from the residues of Apt, Asn, Ndmk, Nmn, and Lys(αAc), -X4 is absent or is an amino acid residue of Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, and Wim, -X6 is an amino acid residue selected from the residues of Gln, Lys(Ac), and Leu, -X8 is an amino acid residue selected from the residues of Yme, Trp, and Yde, -X9 is an amino acid residue of Nal, -X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm, and Thp, -X11 is an amino acid residue selected from the residues of Asp, Glu, Kme, Lys, and Orn, and is bonded to X1 via an amide bond, -X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser, and Ala, -X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His, and Hme, -X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH, or -N(C2H5)2, the compound according to item 5, or a salt or solvate thereof.

[0485] Item 7: A compound of formula (I) wherein - X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad and Dap, which is bonded to X11 via an amide bond, or alternatively, X1 is a residue selected from the residues of Buty and Butyl, which is bonded to X11 via an alkyl bond, and when X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, - R1 is absent or when X1 is a residue selected from the residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C1 - C4 - alkyl or acetyl, which is bonded to the amino functional group of X1, - X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and the corresponding d - forms thereof, - X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, and the corresponding d - forms thereof, X2 and X7 are bonded to each other via Q, where Q is a disulfide bond, a thioether bond or an ester bond, - X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), - X4 is absent or an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr, - X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl, - X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde and Yae, -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, -X12 is either absent or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, -X13 is either absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, Val, and their corresponding d-forms, -X14 is either absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy and Hme, -X15 is either absent or is an amino acid residue of Lys, -R2 is either absent or is -NH2, -OH or -N(C2H5)2, The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, or a salt or solvate thereof, A compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0486] Item 8: -X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, and is bonded to X11 via an amide bond, or Alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond. -R1 is absent or When X1 is a residue selected from the residues of Ahx, Apt and Lys, R1 is H, C1-C4-alkyl or acetyl, and is bonded to the amino functional group of X1. -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, and Thr. -X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu. X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond. -X3 is an amino acid residue selected from the residues of Apt, Asn, Ndmk, Nmn and Lys(αAc). -X4 is absent or is an amino acid residue of Thr. -X5 is an amino acid residue selected from the residues of Trp, Wme and Wim. -X6 is an amino acid residue selected from the residues of Gln, Lys(Ac) and Leu. -X8 is an amino acid residue selected from the residues of Yme, Trp, Yde and Yae. -X9 is an amino acid residue of Nal. -X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm and Thp. -X11 is an amino acid residue selected from the residues of Asp, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond. -X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala. -X13 is either absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His and Hme, -X14 is either absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile and Hme, -X15 is either absent or is the amino acid residue Lys, -R2 is either absent or is -NH2, -OH or -N(C2H5)2, the compound according to item 7, or a salt or solvate thereof.

[0487] Item 9: The compound according to items 1 to 8, wherein R1 is absent.

[0488] Item 10: The compound according to items 1 to 8, wherein R1 is H.

[0489] Item 11: The compound according to items 1 to 8, wherein R1 is C1-C4-alkyl.

[0490] Item 12: The compound according to items 1 to 8, wherein R1 is acetyl.

[0491] Item 13: The compound according to items 1 to 12, wherein R2 is absent.

[0492] Item 14: The compound according to items 1 to 12, wherein R2 is -NH2.

[0493] Item 15: The compound according to items 1 to 12, wherein R2 is -OH.

[0494] Item 16: The compound according to items 1 to 12, wherein R2 is -N(C2H5)2.

[0495] Item 17: X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab and Dap, and X11 is an amino acid residue selected from the residues of Asp and Glu, or or X1 is a residue of Dad, and X11 is an amino acid residue selected from the residues of Lys and Kme, or or The compound according to items 1 to 16, wherein X1 is a residue selected from the residues of Buty or Butyl, and X11 is an amino acid residue of Kme.

[0496] Item 18: The compound according to items 1 to 16, wherein X1 is a residue of Ahx, and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0497] Item 19: The compound according to items 1 to 16, wherein X1 is a residue of Apt, and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0498] Item 20: The compound according to items 1 to 16, wherein X1 is a residue of Apt, and X11 is the amino acid residue Glu.

[0499] Item 21: The compound according to items 1 to 16, wherein X1 is a residue of Nmapt, and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0500] Item 22: The compound according to items 1 to 16, wherein X1 is a residue of Nmapt, and X11 is the amino acid residue Glu.

[0501] Item 23: The compound according to items 1 to 16, wherein X1 is a residue of Nmapt, and X11 is the amino acid residue Asp.

[0502] Item 24: The compound according to items 1 to 16, wherein X1 is a residue of Nmha, and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0503] Item 25: The compound according to items 1 to 16, wherein X1 is a residue of Nmha and X11 is an amino acid residue of Glu.

[0504] Item 26: The compound according to items 1 to 16, wherein X1 is a residue of Nmha and X11 is an amino acid residue of Asp.

[0505] Item 27: The compound according to items 1 to 16, wherein X1 is a residue of Lys and X11 is an amino acid residue selected from the residues of Glu or Asp.

[0506] Item 28: The compound according to items 1 to 16, wherein X1 is a residue of Lys and X11 is an amino acid residue of Glu.

[0507] Item 29: The compound according to items 1 to 16, wherein X1 is a residue of Lys and X11 is an amino acid residue of Asp.

[0508] Item 30: The compound according to items 1 to 16, wherein X1 is a residue of Dad and X11 is an amino acid residue selected from the residues of Lys or Kme.

[0509] Item 31: The compound according to items 1 to 16, wherein X1 is a residue of Dada and X11 is an amino acid residue of Lys.

[0510] Item 32: The compound according to items 1 to 16, wherein X1 is a residue of Dad and X11 is an amino acid residue of Kme.

[0511] Item 33: The compound according to items 1 to 16, wherein X1 is a residue of Buty and X11 is an amino acid residue selected from the residues of Lys or Kme.

[0512] Item 34: The compound according to items 1 to 16, wherein X1 is a residue of Buty and X11 is an amino acid residue of Lys.

[0513] Item 35: The compound according to items 1 to 16, wherein X1 is a residue of Buty and X11 is an amino acid residue of Kme.

[0514] Item 36: The compound according to items 1 to 16, wherein X1 is a residue of Butyl and X11 is an amino acid residue selected from the residues of Lys or Kme.

[0515] Item 37: The compound according to items 1 to 16, wherein X1 is a residue of Butyl and X11 is an amino acid residue of Lys.

[0516] Item 38: The compound according to items 1 to 16, wherein X1 is a residue of Butyl and X11 is an amino acid residue of Kme.

[0517] Item 39: The compound according to items 1 to 38, wherein X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and their corresponding d-forms.

[0518] Item 40: The compound according to items 1 to 38, wherein X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and their corresponding d-forms.

[0519] Item 41: X2 is an amino acid residue selected from the residues of Cys and Nmc, and their corresponding d-forms, X7 is an amino acid residue selected from the residue of Cys and its corresponding d-form, X2 and X7 are linked to each other via Q, where Q is a disulfide bond, Or, X2 is an amino acid residue selected from residues of Cys, Nmc, Thr, and Abu, and their corresponding d-forms, X7 is an amino acid residue selected from residues of Cys, Thr, and Abu, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is a thioether bond, or, X2 is an amino acid residue selected from residues of Glu, Asp, Nmd, Nme, Nmt, and Thr, and their corresponding d-forms, X7 is an amino acid residue selected from residues of Glu, Asp, Thr, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is an ester bond, the compound according to items 1 to 38.

[0520] Item 42: X2 is an amino acid residue selected from residues of Cys and its corresponding d-form, X7 is an amino acid residue selected from residues of Cys and its corresponding d-form, X2 and X7 are linked to each other via Q, where Q is a disulfide bond, or, X2 is an amino acid residue selected from residues of Cys, Glu, Thr, and Abu, and their corresponding d-forms, X7 is an amino acid residue selected from residues of Cys, Thr, and Abu, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is a thioether bond, or, X2 is an amino acid residue selected from residues of Glu and Thr, and their corresponding d-forms, X7 is an amino acid residue selected from residues of Glu, Asp, and Thr, and their corresponding d-forms, X2 and X7 are linked to each other via Q, where Q is an ester bond, the compound according to items 1 to 38.

[0521] Item 43: X2-Q-X7 is Cys-Q-Cys, Nmc-Q-Cys and Cys-Q-Nmc (Q is a disulfide bond), or Abu-Q-Cys, Cys-Q-Abu (Q is a thioether bond), or a compound according to Items 1 to 38 selected from the group consisting of Thr-Q-Asp, Thr-Q-Glu, Glu-Q-Thr (Q is an ester bond).

[0522] Item 44: X2-Q-X7 is -Cys-Q-Cys, Nmc-Q-Cys and Cys-Q-Nmc (Q is a disulfide bond), or -Abu-Q-Cys, Cys-Q-Abu (Q is a thioether bond), or a compound according to Items 1 to 38 selected from the group consisting of -Thr-Q-Asp, Thr-Q-Glu, Glu-Q-Thr (Q is an ester bond).

[0523] Item 45: X2-Q-X7 is -Cys-Q-Cys, Nmc-Q-Cys and Cys-Q-Nmc (Q is a disulfide bond), or -Cys-Q-Abu (Q is a thioether bond), or a compound according to Items 1 to 38 selected from the group consisting of -Thr-Q-Asp, Thr-Q-Glu, Glu-Q-Thr (Q is an ester bond).

[0524] Item 46: X2-Q-X7 is Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond), or Abu-Q-Cys (Q is a thioether bond), or a compound according to Items 1 to 38 selected from the group consisting of Glu-Q-Thr (Q is an ester bond).

[0525] Item 47: The compound according to items 1 to 38, wherein X2-Q-X7 is selected from the group consisting of Cys-Q-Cys and Nmc-Q-Cys (Q is a disulfide bond).

[0526] Item 48: The compound according to items 1 to 38, wherein X2-Q-X7 is Abu-Q-Cys (Q is a thioether bond).

[0527] Item 49: The compound according to items 1 to 38, wherein X2-Q-X7 is Glu-Q-Thr (Q is an ester bond).

[0528] Item 50: The compound according to items 1 to 49, wherein X3 is an amino acid residue selected from the residues of Apt, Ndmk, Nmn and Lys(αAc).

[0529] Item 51: The compound according to items 1 to 49, wherein X3 is the amino acid residue of Sar.

[0530] Item 52: The compound according to items 1 to 49, wherein X3 is the amino acid residue of His.

[0531] Item 53: The compound according to items 1 to 49, wherein X3 is the amino acid residue of Lys.

[0532] Item 54: The compound according to items 1 to 49, wherein X3 is the amino acid residue of Ala.

[0533] Item 55: The compound according to items 1 to 49, wherein X3 is the amino acid residue of Ahx.

[0534] Item 56: The compound according to items 1 to 49, wherein X3 is the amino acid residue of Apt.

[0535] Item 57: The compound according to items 1 to 49, wherein X3 is the amino acid residue of Arg.

[0536] Item 58: The compound according to items 1 to 49, wherein X3 is the amino acid residue of Asn.

[0537] Item 59: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Gab.

[0538] Item 60: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Gln.

[0539] Item 61: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Trp.

[0540] Item 62: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Thr.

[0541] Item 63: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Ndmk.

[0542] Item 64: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Nmn.

[0543] Item 65: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Ntmk.

[0544] Item 66: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Lys(αAc).

[0545] Item 67: The compound according to Items 1 to 66, wherein X4 does not exist.

[0546] Item 68: The compound according to Items 1 to 49, wherein X3 is an amino acid residue selected from the residues of Lys, Ahx, Apt, Thr, Ndmk, Nmn, Ntmk, and Lys(αAc), and X4 does not exist.

[0547] Item 69: The compound according to Items 1 to 49, wherein X3 is an amino acid residue selected from the residues of Apt, Ndmk, Nmn, and Lys(αAc), and X4 does not exist.

[0548] Item 70: The compound according to Items 1 to 49, wherein X3 is an amino acid residue selected from the residues of Apt, Ndmk, and Lys(αAc), and X4 is absent.

[0549] Item 71: The compound according to Items 1 to 49, wherein X3 is an amino acid residue of Lys(αAc), and X4 is absent.

[0550] Item 72: The compound according to Items 1 to 66, wherein X4 is an amino acid residue selected from the residues of His, Lys, Arg, Asn, Gab, Gln, Trp, and Thr.

[0551] Item 73: The compound according to Items 1 to 66, wherein X4 is an amino acid residue selected from the residues of His, Lys, Arg, Asn, Gln, Trp, and Thr.

[0552] Item 74: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of His.

[0553] Item 75: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Lys.

[0554] Item 76: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Ahx.

[0555] Item 77: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Apt.

[0556] Item 78: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Arg.

[0557] Item 79: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Asn.

[0558] Item 80: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Gab.

[0559] Item 81: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Gln.

[0560] Item 82: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Trp.

[0561] Item 83: The compound according to Items 1 to 66, wherein X4 is an amino acid residue of Thr.

[0562] Item 84: The compound according to Items 1 to 83, wherein X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm, and Wfl.

[0563] Item 85: The compound according to Items 1 to 83, wherein X5 is an amino acid residue selected from the residues of Trp, Wme, Wcl, Wim, Wdm, and Wfl.

[0564] Item 86: The compound according to Items 1 to 83, wherein X5 is an amino acid residue selected from the residues of Trp and Wim.

[0565] Item 87: The compound according to Items 1 to 83, wherein X5 is an amino acid residue of Trp.

[0566] Item 88: The compound according to Items 1 to 83, wherein X5 is an amino acid residue of Wme.

[0567] Item 89: The compound according to Items 1 to 83, wherein X5 is an amino acid residue of Nak.

[0568] Item 90: The compound according to Items 1 to 83, wherein X5 is an amino acid residue of Wcl.

[0569] Item 91: The compound according to Items 1 to 83, wherein X5 is an amino acid residue of Wim.

[0570] Item 92: The compound according to Items 1 to 83, wherein X5 is an amino acid residue of Wdm.

[0571] Item 93: The compound according to Items 1 to 83, wherein X5 is an amino acid residue of Wfl.

[0572] Item 94: The compound according to Items 1 to 93, wherein X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp, and Phe.

[0573] Item 94: The compound according to Items 1 to 93, wherein X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, and Val.

[0574] Item 95: The compound according to Items 1 to 93, wherein X6 is an amino acid residue selected from the residues of Gln, Lys(Ac), and Leu.

[0575] Item 96: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Gln.

[0576] Item 97: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Aib.

[0577] Item 98: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Glu.

[0578] Item 99: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Phe.

[0579] Item 100: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Ile.

[0580] Item 101: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Iva.

[0581] Item 102: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Lys.

[0582] Item 103: The compound according to Items 1 to 93, wherein X6 is the amino acid residue Lys(Ac).

[0583] Item 104: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Leu.

[0584] Item 105: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Mle.

[0585] Item 106: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Mly.

[0586] Item 107: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Mva.

[0587] Item 108: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Thr.

[0588] Item 109: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Val.

[0589] Item 110: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Trp.

[0590] Item 111: The compound according to Items 1 to 93, wherein X6 is an amino acid residue of Phe.

[0591] Item 112: The compound according to Items 1 to 111, wherein X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde, and Yae.

[0592] Item 113: The compound according to Items 1 to 111, wherein X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, and Yde.

[0593] Item 114: The compound according to Items 1 to 111, wherein X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde, and Yae.

[0594] Item 115: The compound according to Items 1 to 111, wherein X8 is an amino acid residue selected from the residues of Yme, Yde, and Yae.

[0595] Item 116: The compound according to Items 1 to 111, wherein X8 is an amino acid residue of Yme.

[0596] Item 117: The compound according to Items 1 to 111, wherein X8 is an amino acid residue of Tyr.

[0597] Item 118: The compound according to Items 1 to 111, wherein X8 is an amino acid residue of Trp.

[0598] Item 119: The compound according to Items 1 to 111, wherein X8 is an amino acid residue of Yde.

[0599] Item 120: The compound according to Items 1 to 111, wherein X8 is an amino acid residue of Yae.

[0600] Item 121: The compound according to Items 1 to 111, wherein X9 is an amino acid residue of Nal.

[0601] Item 122: The compound according to Items 1 to 111, wherein X9 is an amino acid of Nak.

[0602] Item 123: The compound according to Items 1 to 111, wherein X9 is an amino acid residue of Trp.

[0603] Item 124: The compound according to Items 1 to 123, wherein X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm, and Thp.

[0604] Item 125: The compound according to Items 1 to 123, wherein X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm, and Thp.

[0605] Item 126: The compound according to Items 1 to 123, wherein X10 is an amino acid residue selected from the residues of Aib, Mle, Mly, Mkdm, and Thp.

[0606] Item 127: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Aib.

[0607] Item 128: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Cba.

[0608] Item 129: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Cit.

[0609] Item 130: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of d-Trp.

[0610] Item 131: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of d-Tza.

[0611] Item 132: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Lys.

[0612] Item 133: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Lys(Ac).

[0613] Item 134: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Leu.

[0614] Item 135: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Mle.

[0615] Item 136: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Mly.

[0616] Item 137: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Gln.

[0617] Item 138: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Mkdm.

[0618] Item 139: The compound according to Items 1 to 123, wherein X10 is an amino acid residue of Thp.

[0619] Item 140: The compound according to Items 1 to 139, wherein X12 is absent or is an amino acid residue selected from residues of Asn, Ser, and Ala.

[0620] Item 141: The compound according to Items 1 to 139, wherein X12 is absent.

[0621] Item 142: The compound according to Items 1 to 139, wherein X12 is the amino acid residue of Asn.

[0622] Item 143: The compound according to Items 1 to 139, wherein X12 is the amino acid residue of Ser.

[0623] Item 144: The compound according to Items 1 to 139, wherein X12 is the amino acid residue of Ala.

[0624] Item 145: The compound according to Items 1 to 144, wherein X13 is absent or is an amino acid residue selected from residues of Asn, Ala, Bal, Gly, Leu, d-Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, Val, and their corresponding d-forms.

[0625] Item 146: The compound according to Items 1 to 144, wherein X13 is absent or is an amino acid residue selected from residues of Asn, Ala, Bal, Gly, Leu, d-Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, and Val.

[0626] Item 147: The compound according to Items 1 to 144, wherein X13 is absent.

[0627] Item 148: The compound according to Items 1 to 144, wherein X13 is the amino acid residue of Asn.

[0628] Item 149: The compound according to Items 1 to 144, wherein X13 is the amino acid residue of Ala.

[0629] Item 150: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Bal.

[0630] Item 151: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Gly.

[0631] Item 152: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Leu.

[0632] Item 153: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of d-Leu.

[0633] Item 154: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Ile.

[0634] Item 155: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Iva.

[0635] Item 156: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Hol.

[0636] Item 157: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Hph.

[0637] Item 158: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Pal.

[0638] Item 159: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Pyal.

[0639] Item 160: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of PyEA.

[0640] Item 161: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of His.

[0641] Item 162: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Hme.

[0642] Item 163: The compound according to Items 1 to 144, wherein X13 is an amino acid residue of Val.

[0643] Item 164: The compound according to Items 1 to 163, wherein X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy, and Hme.

[0644] Item 165: The compound according to Items 1 to 163, wherein X14 is absent.

[0645] Item 166: The compound according to Items 1 to 163, wherein X14 is an amino acid residue of Mep.

[0646] Item 167: The compound according to Items 1 to 163, wherein X14 is an amino acid residue of Sar.

[0647] Item 168: The compound according to Items 1 to 163, wherein X14 is an amino acid residue of Bal.

[0648] Item 169: The compound according to Items 1 to 163, wherein X14 is an amino acid residue of Ile.

[0649] Item 170: The compound according to Items 1 to 163, wherein X14 is an amino acid residue of Dnmy.

[0650] Item 171: The compound according to Items 1 to 163, wherein X14 is an amino acid residue of Hme.

[0651] Item 172: The compound according to Items 1 to 171, wherein X15 is absent.

[0652] Item 172: The compound according to Items 1 to 171, wherein X15 is Lys.

[0653] Item 173: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Gln-Cys.

[0654] Item 174: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Wim-Gln-Cys.

[0655] Item 175: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Trp-Lys(Ac)-Cys.

[0656] Item 176: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Cys-Asn-Thr-Wim-Lys(Ac)-Cys.

[0657] Item 177: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Cys-Nmn-Thr-Trp-Gln-Cys.

[0658] Item 178: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Abu-Asn-Thr-Trp-Lys(Ac)-Cys.

[0659] Item 179: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Abu-Asn-Thr-Wim-Lys(Ac)-Cys.

[0660] Item 180: The compound according to Items 1 to 172, wherein X2-X3-X4-X5-X6-X7 is Abu-Asn-Thr-Wme-Leu-Cys.

[0661] Item 181: X12-X13- is Gly-PyEA, X14 does not exist, X15 does not exist, R2 does not exist, the compound according to Items 1 to 180.

[0662] Item 182: The compound according to Items 1 to 181, wherein X8-X9-X10 is Yde-Nal-X10 and X10 is selected from the residues of Aib, Mle, Thp, Mkdm or Mly.

[0663] Item 183: Formula (Ia)

Chemical formula

[0664] Item 184: In the compound of formula (Ia), X2 is, Amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and amino acid residues selected from the corresponding d-forms thereof, wherein X8 is an amino acid residue selected from the amino acid residues of Yme, Tyr, Trp and Yde, or or, amino acid residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and amino acid residues selected from the corresponding d-forms thereof, wherein X8 is an amino acid residue selected from the amino acid residues of Yme, Tyr, TrP, Yde and Yae, which is any one of the compounds described in item 183.

[0665] Item 185: The compound described in item 183, wherein when X2 of the compound of formula (Ia) is Abu or its corresponding d-form, X8 is not an amino acid residue of Yae.

[0666] Item 186: The compound described in item 183, wherein when X8 of the compound of formula (Ia) is Yae, X2 is not an amino acid residue of Abu or its corresponding d-form.

[0667] Item 187: The compound of formula (Ia) is - X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad and Dap, and is bonded to X11 via an amide bond, or or, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, - R1 is absent, or when X1 is a residue selected from the residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C1-C4-alkyl or acetyl, and is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and their corresponding d-forms, -X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, and their corresponding d-forms, X2 and X7 are bonded to each other via Q, where Q is a disulfide bond, a thioether bond or an ester bond, -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), -X4 is either absent or an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp and Yde, -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, -X12 is either absent or an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, -X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, Val, and the corresponding d-forms thereof, -X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH or -N(C2H5)2, The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, At least one of X10 and X15 is an amino acid residue having a side chain with an -NH2 group, and the -NH2 side chain group is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5 or R5, and R5 is a moiety optionally containing up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O, S and P, or a salt or solvate thereof, The compound according to item 183, wherein the compound of formula (Ia) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0668] Item 189: The compound of formula (Ia) is -X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pipa, Pipb, Pipp, Dab, Dad and Dap, and is bonded to X11 via an amide bond, or X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is absent or When X1 is a residue selected from the residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C1-C4-alkyl or acetyl, which is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and their corresponding d-forms, -X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, and their corresponding d-forms, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), -X4 is absent or is an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde and Yae, -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is bonded to -X1 via an amide bond, -X12 is absent or is an amino acid residue selected from residues of Asn, Gly, Ser, and Ala, -X13 is absent or is an amino acid residue selected from residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, PyAl, PyEA, His, Hme, Val, and amino acid residues selected from the corresponding d-forms thereof, -X14 is absent or is an amino acid residue selected from residues of Mep, Sar, Bal, Ile, Dnmy, and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or is -NH2, -OH, or -N(C2H5)2, The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, At least one of X10 and X15 is an amino acid residue having a side chain with an -NH2 group, and the -NH2 side chain group is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5, or R5, where R5 is a moiety optionally containing up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O, S, and P, or a salt or solvate thereof, The compound according to item 183, wherein the compound of formula (Ia) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

[0669] Item 190: The compound according to items 183 to 189, wherein at least one of X10 and X15 is an amino acid residue having a side chain with an -NH2 group, and the -NH2 side chain group is functionalized by -C(O)-R5, where R5 is a moiety optionally containing up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O, S, and P.

[0670] Item 191: X10 is an amino acid residue selected from the residues of Lys and Mly, X15 is absent, the -NH2 side chain group of X10 is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5 or R5, for example, by -C(O)-R5, and R5 may be a moiety containing up to 50 or up to 100 carbon atoms, and optionally heteroatoms selected from halogen, N, O, S and P, The compound of formula (Ia) inhibits the binding of interleukin-23 to the interleukin-23 receptor. Compounds of items 183 to 190.

[0671] Item 192: X10 is an amino acid residue selected from the residues of Lys and Mly, X15 is Lys, the -NH2 side chain group of X15 is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O)2-R5 or R5, for example, by -C(O)-R5, and R5 may be a moiety containing up to 50 or up to 100 carbon atoms, and optionally heteroatoms selected from halogen, N, O, S and P, The compound of formula (Ia) inhibits the binding of interleukin-23 to the interleukin-23 receptor, compounds of items 183 to 190.

[0672] Item 193: The compound according to item 191 or 192, wherein the -NH2 side chain group of X10 or X15 is functionalized by -C(O)-R5.

[0673] Item 194: -C(O)-R5 is (S)-4-carboxy-4-hexadecanoylamino-butyryl-, (S)-4-carboxy-4-octadecanoylamino-butyryl-, 4-hexadecanoylamino-butyryl-, 4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, 4-octadecanoylamino-butyryl-, 4-((Z)-octadec-9-enoylamino)-butyryl-, 6-[(4,4-diphenyl-cyclohexyloxy)-hydroxy-phosphoryloxy]-hexanoyl-, hexadecanoyl-, (S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyryl-, (S)-4-carboxy-4-{3-[3-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-propionylamino]-propionylamino}-butyryl-, (S)-4-carboxy-4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, (S)-4-carboxy-4-((9Z,12Z)-octadeca-9,12-dienoylamino)-butyryl-, (S)-4-carboxy-4-[6-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-hexanoylamino]-butyryl-, (S)-4-carboxy-4-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-butyryl-, (S)-4-carboxy-4-tetradecanoylamino-butyryl-, (S)-4-(11-benzyloxycarbonyl-undecanoylamino)-4-carboxy-butyryl-, (S)-4-carboxy-4-[11-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxy-hexylcarbamoyl)-undecanoylamino]-butyryl-, (S)-4-carboxy-4-((Z)-octadec-9-enoylamino)-butyryl-, (S)-4-carboxy-4-(4-dodecyloxy-benzoylamino)-butyryl-,(S)-4-Carboxy-4-henicosanoylamino-butyryl-, (S)-4-carboxy-4-docosanoylamino-butyryl-, (S)-4-carboxy-4-((Z)-nonadec-10-enoylamino)-butyryl-, (S)-4-carboxy-4-(4-decyloxy-benzoylamino)-butyryl-, (S)-4-carboxy-4-[(4’-octyloxy-biphenyl-4-carbonyl)amino]-butyryl-, (S)-4-carboxy-4-(12-phenyl-dodecanoylamino)-butyryl-, (S)-4-carboxy-4-icosanoylamino-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-hexadecanoylbutyrylamino-butyrylamino)-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-octadecanoylbutyrylamino-butyrylamino)-butyryl-, 3-(3-octadecanoylamino-propionylamino)-propionyl-, 3-(3-hexadecanoylamino-propionylamino)-propionyl-, 3-hexadecanoylamino-propionyl-, (S)-4-carboxy-4-[(R)-4-((3R,5S,7R,8R,9R,10S,12S,13R,14R,17R)-3,7,12-trihydroxy-8,10,13-trimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-carboxy-4-[(R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-carboxy-4-((9S,10R)-9,10,16-trihydroxy-hexadecanoylamino)-butyryl-, tetradecanoyl-, 11-carboxy-undecanoyl-, 11-benzyloxycarbonyl-undecanoyl-, (S)-4-carboxy-4-((S)-4-carboxy-4-tetradecanoylamino-butyrylamino)-butyryl-, 6-[hydroxy-(naphthalen-2-yloxy)-phosphoryloxy]-hexanoyl-, 6-[hydroxy-(5-phenyl-pentyloxy)-phosphoryloxy]-hexanoyl-,4-(naphthalene-2-sulfonylamino)-4-oxo-butyryl-, 4-(biphenyl-4-sulfonylamino)-4-oxo-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-acetylamino]-butyryl-, (S)-4-carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-,(S)-4-Carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetyl, (S)-4-carboxy-4-((S)-4-carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-butyrylamino}-butyrylamino)-butyryl, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(16-1H-tetrazol-5-yl-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(16-carboxy-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxy-phenoxy)-decanoylamino]-butyrylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(7-carboxy-heptanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-,(S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(11-carboxy-undecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(13-carboxy-tridecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, and (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, a compound according to item 193, selected from the group consisting of.

[0674] Item 195. A compound according to items 1 to 194, having a binding affinity for the interleukin-23 receptor of 100 nM or less (i.e., IC 50 ≦100 nM).

[0675] Item 196. A compound according to items 1 to 194, having a binding affinity for the interleukin-23 receptor of 50 nM or less (i.e., IC 50 ≦50 nM).

[0676] Item 197. A compound according to items 1 to 194, having a binding affinity for the interleukin-23 receptor of 10 nM or less (i.e., IC 50 ≦10 nM).

[0677] Item 198. A compound of Items 1 to 194 having a binding affinity for interleukin 23 receptor of 5 nM or less (i.e., IC 50 ≦ 5 nM).

[0678] Item 199. A compound of Items 1 to 194 having chemical stability with a relative purity loss of less than 30% over 24 hours at 37 °C in a solution at pH 1.2.

[0679] Item 200. A compound of Items 1 to 194 having chemical stability with a relative purity loss of less than 25% over 24 hours at 37 °C in a solution at pH 1.2.

[0680] Item 201. A compound of Items 1 to 194 having chemical stability with a relative purity loss of less than 5% over 24 hours at 37 °C in a solution at pH 6.5.

[0681] Item 202. A compound of Items 1 to 194 having chemical stability with a relative purity loss of less than 2% over 24 hours at 37 °C in a solution at pH 6.5.

[0682] Item 203. A compound of Items 1 to 194 having chemical stability with a relative purity loss of less than 5% over 24 hours at 37 °C in a solution at pH 7.4.

[0683] Item 204. A compound of Items 1 to 194 having chemical stability with a relative purity loss of less than 3% over 24 hours at 37 °C in a solution at pH 7.4.

Claims

1. A compound of formula (I): 【Chemical 1】 wherein -X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmapt, Lys, Pip a, Pip b, Pipp, Dab, Dad and Dap, and is bonded to X11 via an amide bond, or X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue selected from the residues of Butyl, the residue selected from the residues of Butyl is bonded to X2 via an alkyl bond, -R1 is absent or -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr and Abu, and the corresponding d-forms thereof, When X1 is a residue selected from the residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C １ ~C ４ -alkyl or acetyl, which is bonded to the amino functional group of X1, -X7 is an amino acid residue selected from Cys, Glu, Asp, Thr and Abu, and the corresponding d-forms thereof, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), -X4 is absent or an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp and Yde, -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkd m and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, ​ -X12 is absent or is an amino acid residue selected from residues of Asn, Gly, Ser, and Ala, -X13 is absent or is an amino acid residue selected from residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, and Val, and amino acid residues selected from their corresponding d-forms, -X14 is absent or is an amino acid residue selected from residues of Mep, Sar, Bal, Ile, Dnmy, and Hme, X15 is absent or is an amino acid residue selected from residues of Lys, -R2 is absent or -NH ２ , -OH or -N(C ２ H ５ ) ２ and is The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, A compound or a salt or solvate thereof, A compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

2. -X1 is a residue selected from residues of Ahx, Apt, Nmha, Nmapt, Lys, and Dad, and is bonded to X11 via an amide bond, or X1 is a residue selected from residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is absent or when X1 is a residue selected from residues of Ahx, Apt, and Lys, R1 is H, C1-C4-alkyl, or acetyl, and is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr, and Abu, -X7 is an amino acid residue selected from residues of Cys, Glu, Asp, Thr, and Abu, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond, or an ester bond, -X3 is an amino acid residue selected from residues of Apt, Asn, Ndmk, Nmn, and Lys(αAc), -X4 is absent or is an amino acid residue of Thr, -X5 is an amino acid residue selected from residues of Trp, Wme, and Wim, -X6 is an amino acid residue selected from residues of Gln, Lys(Ac), and Leu, -X8 is an amino acid residue selected from residues of Yme, Trp and Yde, -X9 is an amino acid residue of Nal, -X10 is an amino acid residue selected from residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkdm and Thp, -X11 is an amino acid residue selected from residues of Asp, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, -X12 is either absent or is an amino acid residue selected from residues of Asn, Gly, Ser and Ala, -X13 is either absent or is an amino acid residue selected from residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His and Hme, -X14 is either absent or is an amino acid residue selected from residues of Mep, Sar, Bal, Ile and Hme, -X15 is either absent or is an amino acid residue of Lys, -R2 is either absent or is -NH2, -OH or -N(C2H5)2, the compound of formula (I) according to claim 1.

3. Formula (I): 【Chemical Formula 2】 a compound of wherein -X1 is a residue selected from residues of Ahx, Aoa, Apt, Nmha, Nmap t, Lys, Pipa, Pipb, Pipp, Dab, Dad and Dap, and is bonded to X11 via an amide bond, or, X1 is a residue selected from residues of Buty and Butyl, and is bonded to X11 via an alkyl bond, and when X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is either absent or When X1 is a residue selected from the residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C １ ~C ４ -alkyl or acetyl, which is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and amino acid residues selected from their corresponding d-forms, -X7 is an amino acid residue selected from residues of Cys, Glu, Asp, Thr and Abu, and amino acid residues selected from their corresponding d-forms, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, -X3 is an amino acid residue selected from residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), -X4 is absent or is an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde and Yae, -X9 is an amino acid residue selected from the residues of Nal, Nak and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys and Orn, and is bonded to X1 via an amide bond, -X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser and Ala, -X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, Val, and their corresponding d-forms, -X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy and Hme, -X15 is absent or is an amino acid residue of Lys, -R2 is absent or -NH ２ , -OH or -N(C ２ H ５ ) ２ and The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated. A compound or a salt or solvate thereof, wherein the compound of formula (I) inhibits the binding of interleukin-23 to the interleukin-23 receptor. A compound or a salt or solvate thereof.

4. -X1 is a residue selected from the residues of Ahx, Apt, Nmha, Nmapt, Lys and Dad, and is bonded to X11 via an amide bond, or Alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond. - R1 is absent or When X1 is a residue selected from residues of Ahx, Apt and Lys, R1 is H, C １ ~C ４ -alkyl or acetyl, which is bonded to the amino functional group of X1, - X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, and Thr. - X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr, and Abu. X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond, or an ester bond. - X3 is an amino acid residue selected from the residues of Apt, Asn, Ndmk, Nmn, and Lys(αAc). - X4 is absent or is an amino acid residue of Thr. - X5 is an amino acid residue selected from the residues of Trp, Wme, and Wim. - X6 is an amino acid residue selected from the residues of Gln, Lys(Ac), and Leu. - X8 is an amino acid residue selected from the residues of Yme, Trp, Yde, and Yae. - X9 is an amino acid residue of Nal. - X10 is an amino acid residue selected from the residues of Aib, Lys, Lys(Ac), Mle, Mly, Mkd m, and Thp. - X11 is an amino acid residue selected from the residues of Asp, Glu, Kme, Lys, and Orn, and is bonded to X1 via an amide bond. - X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser, and Ala. - X13 is absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, d-Leu, Ile, Pal, Pyal, PyEA, His, and Hme. - X14 is absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, and Hme. - X15 is absent or is the amino acid residue Lys. -R2 is absent or -NH ２ , -OH or -N(C ２ H ５ ), the compound of formula (I) according to claim 3, wherein: ２ ​

5. - X3 is an amino acid residue selected from the residues of Asn and Nmn. - X4 is an amino acid residue of Thr. The compound of formula (I) according to any one of claims 1 to 4.

6. - X3 is an amino acid residue selected from the residues of Ndmk and Lys(αAc). - X4 is absent. The compound of formula (I) according to any one of claims 1 to 4.

7. - X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmap t, Lys, Pip a, Pip b, Pipp, Dab and Dap, and X11 is an amino acid residue selected from the residues of Asp and Glu, or or, - X1 is a residue of Dad, and X11 is an amino acid residue selected from the residues of Lys and Kme, or or, - X1 is a residue selected from the residues of Buty and Butyl, and X11 is an amino acid residue of Kme, the compound of formula (I) according to claim 1 or 3.

8. X2 - Q - X7 is Q is a disulfide bond, -Cys - Q - Cys, Nmc - Q - Cys and Cys - Q - Nmc, or Q is a thioether bond, - Abu - Q - Cys, Cys - Q - Abu, or Q is an ester bond, - Thr - Q - Asp, Thr - Q - Glu, Glu - Q - Thr, the group of the compound of formula (I) according to claim 1.

9. X2 - Q - X7 is Q is a disulfide bond, -Cys - Q - Cys, Nmc - Q - Cys and Cys - Q - Nmc, or Q is a thioether bond, - Cys - Q - Abu, or Q is an ester bond, - Thr - Q - Asp, Thr - Q - Glu, Glu - Q - Thr, the group of the compound of formula (I) according to claim 3.

10. - R1 is absent or is H, C １ ~ C ４ - alkyl or acetyl, and is bonded to the amino functional group of X1, - X1 is a residue of Apt, and is bonded to X11 via an amide bond, - X2 is an amino acid residue of Cys, - X7 is an amino acid residue of Cys, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, - X3 is an amino acid residue selected from the residues of Asn and Lys(αAc), - X4 is absent or is an amino acid residue of Thr, - X5 is an amino acid residue of Wim, - X6 is an amino acid residue of Lys(Ac), - X8 is an amino acid residue of Yde, - X9 is an amino acid residue of Nal, - X10 is an amino acid residue selected from the residues of Mkdm and Thp, - X11 is an amino acid residue of Glu, and is bonded to - X1 via an amide bond, - X12 is an amino acid residue of Asn, - X13 is an amino acid residue of Pal, - X14 is an amino acid residue of Sar, - X15 does not exist, -R2 is -NH ２ and The compound of formula (I) according to claim 1 or 3, wherein the compound inhibits the binding of interleukin-23 to the interleukin-23 receptor.

11. - X1 is a residue selected from the residues of Ahx, APT, Nmha, Nmapt, Lys and Dad, and is bonded to -X11 via an amide bond, or or, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, - R1 is absent, or When X1 is a residue selected from residues of Ahx, Apt and Lys, R1 is H, C １ ~C ４ -alkyl or acetyl, which is bonded to the amino functional group of -X1, - X2 is an amino acid residue selected from the residues of Cys, Nmc and Abu, - X7 is an amino acid residue selected from the residues of Cys, Glu, Asp and Thr, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, - X3 is an amino acid residue of Lys(αAc), - X4 is absent, - X5 is an amino acid residue selected from the residues of Trp and Wim, - X6 is an amino acid residue of Lys(Ac), - X8 is an amino acid residue of Yde, - X9 is an amino acid residue of Nal, - X10 is an amino acid residue selected from the residues of Mkdm and Thp, - X11 is an amino acid residue selected from the residues of Asp, Glu, Kme and Lys, and is bonded to X1 via an amide bond, - X12 is an amino acid residue of Gly, - X13 is an amino acid residue of PyEA, - X14 is absent, - X15 is absent, - R2 is absent. The compound of formula (I) according to any one of claims 1, 2 and 6.

12. The compound of formula (I) according to claim 1, wherein the compound is selected from the compounds of SEQ ID NO: 1 to 66, SEQ ID NO: 68 to 70, SEQ ID NO: 72 to 74, SEQ ID NO: 76 to 82, SEQ ID NO: 84 to 95, SEQ ID NO: 98, SEQ ID NO: 102 to 106, SEQ ID NO: 108 to 158.

13. Compound of formula (Ia): 【Chemical 3】 wherein in the formula, - X1 is a residue selected from the residues of Ahx, Aoa, APT, Nmha, Nmapt, Lys, Pip a, Pip b, Pipp, Dab, Dad and Dap, and is bonded to X11 via an amide bond, or Alternatively, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond. - R1 is absent or When X1 is a residue selected from residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C １ ~C ４ -alkyl or acetyl, which is bonded to the amino functional group of X1, - X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt, Thr, and Abu, and their corresponding d-forms. - X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr, and Abu, and their corresponding d-forms. X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond, or an ester bond. - X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk, and Lys(αAc). - X4 is absent or is an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, and Thr. - X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm, and Wfl. - X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp, and Phe. - X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, and Yde. - X9 is an amino acid residue selected from the residues of Nal, Nak, and Trp. - X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm, and Thp. - X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys, and Orn, and is bonded to X1 via an amide bond. - X12 is absent or is an amino acid residue selected from the residues of Asn, Gly, Ser, and Ala. -X13 is either absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, Val, and the corresponding d-forms thereof, -X14 is either absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy and Hme, -X15 is either absent or is an amino acid residue of Lys, -R2 is absent or -NH ２ , -OH or -N(C ２ H ５ ) ２ and is The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated, At least one of X10 and X15 is an amino acid residue having a side chain with an -NH ２ group, and the -NH ２ side chain group is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O) ２ -R5 or R5, and R5 is a moiety that may contain up to 50 or up to 100 carbon atoms, and optionally a heteroatom selected from halogen, N, O, S, and P A compound or a salt or solvate thereof, A compound or a salt or solvate thereof, wherein the compound of formula (Ia) inhibits the binding of interleukin-23 to the interleukin-23 receptor.

14. Formula (Ia): [Chemical Formula 4] A compound of Wherein -X1 is a residue selected from the residues of Ahx, Aoa, Apt, Nmha, Nmap, Lys, Pipa, Pipb, Pipp, Dab, Dad and Dap, and is bonded to X11 via an amide bond, Or, X1 is a residue selected from the residues of Buty and Butyl, and is bonded to X11 via an alkyl bond. When X1 is a residue of Butyl, the residue of Butyl is bonded to X2 via an alkyl bond, -R1 is either absent or When X1 is a residue selected from residues of Ahx, Aoa, Apt, Lys, Dab and Dap, R1 is H, C １ ~C ４ -alkyl or acetyl, which is bonded to the amino functional group of X1, -X2 is an amino acid residue selected from the residues of Cys, Glu, Asp, Nmc, Nmd, Nme, Nmt and Thr, and the corresponding d-forms thereof, -X7 is an amino acid residue selected from the residues of Cys, Glu, Asp, Thr and Abu, and the corresponding d-forms thereof, X2 and X7 are bonded to each other via Q, and Q is a disulfide bond, a thioether bond or an ester bond, -X3 is an amino acid residue selected from the residues of Sar, His, Lys, Ala, Ahx, Apt, Arg, Asn, Gab, Gln, Trp, Thr, Ndmk, Nmn, Ntmk and Lys(αAc), -X4 is either absent or is an amino acid residue selected from the residues of His, Lys, Ahx, Apt, Arg, Asn, Gab, Gln, Trp and Thr, -X5 is an amino acid residue selected from the residues of Trp, Wme, Nak, Wcl, Wim, Wdm and Wfl, -X6 is an amino acid residue selected from the residues of Gln, Aib, Glu, Phe, Ile, Iva, Lys, Lys(Ac), Leu, Mle, Mly, Mva, Thr, Val, Trp, and Phe, -X8 is an amino acid residue selected from the residues of Yme, Tyr, Trp, Yde, and Yae, -X9 is an amino acid residue selected from the residues of Nal, Nak, and Trp, -X10 is an amino acid residue selected from the residues of Aib, Cba, Cit, d-Trp, d-Tza, Lys, Lys(Ac), Leu, Mle, Mly, Gln, Mkdm, and Thp, -X11 is an amino acid residue selected from the residues of Asp, Bal, Gab, Glu, Kme, Lys, and Orn, and is bonded to -X1 via an amide bond, -X12 is either absent or is an amino acid residue selected from the residues of Asn, Gly, Ser, and Ala, -X13 is either absent or is an amino acid residue selected from the residues of Asn, Ala, Bal, Gly, Leu, Ile, Iva, Hol, Hph, Pal, Pyal, PyEA, His, Hme, Val, and amino acid residues selected from their corresponding d-forms, -X14 is either absent or is an amino acid residue selected from the residues of Mep, Sar, Bal, Ile, Dnmy, and Hme, -X15 is either absent or is an amino acid residue of Lys, R2 is absent or -NH ２ , -OH or -N(C ２ H ５ ) ２ and is The amide bonds between X1 and X2, between X2 and X3, between X3 and X4, between X4 and X5, and between X11 and X1 are optionally methylated. At least one of X10 and X15 is an amino acid residue having a side chain with an -NH ２ group, and the -NH ２ side chain group is functionalized by -C(O)-R5, -C(O)O-R5, -C(O)NH-R5, -S(O) ２ -R5 or R5, and R5 is a moiety that may contain up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O, S, and P A compound or a salt or solvate thereof, wherein the compound of formula (Ia) inhibits the binding of interleukin-23 to the interleukin-23 receptor. A compound or a salt or solvate thereof.

15. -X10 is a residue selected from residues of Lys and Mly, said -NH ２ the side chain group is functionalized by -C(O)-R5, and -X15 is absent or -X15 is Lys, and the -NH ２ side chain group is functionalized by -C(O)-R5, -C(O)-R5 is (S)-4-carboxy-4-hexadecanoylamino-butyryl-, (S)-4-carboxy-4-octadecanoylamino-butyryl-, 4-hexadecanoylamino-butyryl-, 4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, 4-octadecanoylamino-butyryl-, 4-((Z)-octadec-9-enoylamino)-butyryl-, 6-[(4,4-diphenyl-cyclohexyloxy)-hydroxy-phosphoryloxy]-hexanoyl-, hexadecanoyl-, (S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyryl-, (S)-4-carboxy-4-{3-[3-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-propionylamino]-propionylamino}-butyryl-, (S)-4-carboxy-4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, (S)-4-carboxy-4-((9Z,12Z)-octadeca-9,12-dienoylamino)-butyryl-, (S)-4-carboxy-4-[6-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-hexanoylamino]-butyryl-, (S)-4-carboxy-4-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-butyryl-, (S)-4-carboxy-4-tetradecanoylamino-butyryl-, (S)-4-(11-benzyloxycarbonyl-undecanoylamino)-4-carboxy-butyryl-, (S)-4-carboxy-4-[11-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxy-hexylcarbamoyl)-undecanoylamino]-butyryl-, (S)-4-carboxy-4-((Z)-octadec-9-enoylamino)-butyryl-, (S)-4-carboxy-4-(4-dodecyloxy-benzoylamino)-butyryl-(S)-4-Carboxy-4-henicosanoylamino-butyryl-, (S)-4-carboxy-4-docosanoylamino-butyryl-, (S)-4-carboxy-4-((Z)-nonadec-10-enoylamino)-butyryl-, (S)-4-carboxy-4-(4-decyloxy-benzoylamino)-butyryl-, (S)-4-carboxy-4-[(4'-octyloxy-biphenyl-4-carbonyl)amino]-butyryl-, (S)-4-carboxy-4-(12-phenyl-dodecanoylamino)-butyryl-, (S)-4-carboxy-4-icosanoylamino-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl-, 3-(3-octadecanoylamino-propionylamino)-propionyl-, 3-(3-hexadecanoylamino-propionylamino)-propionyl-, 3-hexadecanoylamino-propionyl-, (S)-4-carboxy-4-[(R)-4-((3R,5S,7R,8R,9R,10S,12S,13R,14R,17R)-3,7,12-trihydroxy-8,10,13-trimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-carboxy-4-[(R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-carboxy-4-((9S,10R)-9,10,16-trihydroxy-hexadecanoylamino)-butyryl-, tetradecanoyl-, 11-carboxy-undecanoyl-, 11-benzyloxycarbonyl-undecanoyl-, (S)-4-carboxy-4-((S)-4-carboxy-4-tetradecanoylamino-butyrylamino)-butyryl-, 6-[hydroxy-(naphthalen-2-yloxy)-phosphoryloxy]-hexanoyl-, 6-[hydroxy-(5-phenyl-pentyloxy)-phosphoryloxy]-hexanoyl-4-(Naphthalene-2-sulfonylamino)-4-oxo-butyryl-, 4-(Biphenyl-4-sulfonylamino)-4-oxo-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}butyryl-, (S)-4-carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy)-acetylamino]-butyryl-, (S)-4-carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-,(S)-4-carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetyl, (S)-4-carboxy-4-((S)-4-carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-butyrylamino})-butyryl, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(16-1H-tetrazol-5-yl-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(16-carboxy-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-((S)-4-carboxy-4-{2-[2-(2-{2-[2-(2-{((S)-4-carboxy-4-[10-(4-carboxy-phenoxy)-decanoylamino]-butyrylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(7-carboxy-heptanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-(S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(11-carboxy-undecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(13-carboxy-tridecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, and (S)-4-carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, a compound of formula (Ia) according to claim 13 or 14, selected from the group consisting of.

16. -C(O)-R5 is selected from tetradecanoyl, hexadecanoyl, and 2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-. The compound of formula (Ia) according to claim 13 or 15.

17. The compound according to any one of claims 1 to 17, represented by SEQ ID NOs: 1 to 158.

18. The compound according to claim 13 or 15, represented by SEQ ID NO: 67, 71, 75, 83, 96, 97, 99, 100, 101 and 108.

19. The compound according to claim 1 or 3, represented by SEQ ID NO: 35, 66, 113, 128, 144, 146, 147, 147, 148 and 149.

20. A compound for use according to any one of claims 1 to 20 for the treatment of an autoimmune disease or an inflammatory disease.

21. The compound for use according to claim 21, wherein the autoimmune disease or inflammatory disease is selected from inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, psoriasis, psoriatic arthritis and hidradenitis suppurativa.

22. A compound for use according to any one of claims 1 to 20, present as an active agent in a pharmaceutical composition together with at least one pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising at least one compound according to any one of claims 1 to 20, or a physiologically acceptable salt or solvate thereof, and at least a pharmaceutically acceptable carrier for use as a medicine.

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