Oral peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory bowel diseases

A peptide, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide comprises the amino acid sequence of Formula (Xa):

• X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20 (Xa)
• wherein
• X1 is any amino acid or absent;
• X2 is any amino acid or absent;
• X3 is any amino acid or absent;
• X4 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Sec, 2-chloromethylbenzoic acid, mercapto-propanoic acid, mercapto-butyric acid, 2-chloro-acetic acid, 3-choro-propanoic acid, 4-chloro-butyric acid, 3-chloro-isobutyric acid, Abu, β-azido-Ala-OH, propargylglycine, 2-(3′-butenyl)glycine, 2-allylglycine, 2-(3′-butenyl)glycine, 2-(4′-pentenyl)glycine, 2-(5′-hexenyl)glycine, or absent;
• X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D-Leu, D-Thr, D-Ser, α-MeOrn, α-MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn, or Gln;
• X6 is any amino acid;
• X7 is any amino acid;
• X8 is any amino acid;
• X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, Ser, Sec, Abu, β-azido-Ala-OH, propargylglycine, 2-2-allylglycine, 2-(3′-butenyl)glycine, 2-(4′-pentenyl)glycine, Ala, hCys, Met, MeCys, (D) Tyr, or 2-(5′-hexenyl)glycine;
• X10 is Phe, Tyr, a Phe analog, or a Tyr analog;
• X11 is Trp, 1-Nal, 2-Nal, Phe (3,4-OMe2) 5-Hydroxy-Trp, Phe (3,4-Cl2), or Tyr (3-t-Bu);
• X12 is His, Phe, Arg, N-Me-His, or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala, t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Agp, Aib, α-DiethylGly, α-MeLys, α-MeLys (Ac), α-Me-Leu, α-MeOrn, α-MeSer, α-MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;
• X13 is Cit, Asp, Dab, Dap, Phe, His, Dap (Peg2-Ac), Dap (pyroglutaric acid), hArg, Lys, Lys (Ac), Lys (Benzoic acid), Lys (glutaric acid), Lys (IVA), Lys (Peg4- isoGlu-Palm), Lys (pyroglutaric acid), Lys (succinic acid), Asn, Orn, Gln, Arg, Thr or Val, wherein Lys (IVA) is
• X14 is Phe, Tyr, BhPhe, Asn, Arg, Gln, Lys (Ac), His;
• Dap (Ac), Dab (Ac), or Asp;
• X15 is any amino acid,
• X16 is any amino acid or absent;
• X17 is any amino acid or absent;
• X18 is any amino acid or absent;
• X19 is any amino acid or absent;
• and
• X20 is any amino acid or absent,
• wherein the peptide is cyclized via a bond between two amino acid residues within the peptide.