Claims

1. A method of treatment of inflammatory bowel disease, comprising the step of administering an effective amount of an inhibitor of a C5a receptor to a subject in need of such treatment, in which the inhibitor is a compound thatis an antagonist of a C5a receptor,andis a cyclic peptide or peptidomimetic compound of formula I: ##STR00002## where A is H, alkyl, aryl, NH₂, NH-alkyl, N(alkyl)₂, NH-aryl, NH-acyl, NH-benzoyl, NHSO₃, NHSO_2-alkyl, NHSO_2-aryl, OH, O-alkyl, or O-aryl;B is an alkyl, aryl, phenyl, benzyl, naphthyl or indole group, or the side chain of a D- or L-amino acid, but is not the side chain of glycine, D-phenylalanine, L-homophenylalanine, L-tryptophan, L-homotryptophan, L-tyrosine, or L-homotyrosine;C is the side chain of a D-, L- or homo-amino acid, but is not the side chain of isoleucine, phenylalanine, or cyclohexylalanine;D is the side chain of a neutral D-amino acid, but is not the side chain of glycine or D-alanine, a bulky planar side chain, or a bulky charged side chain;E is a bulky substituent, but is not the side chain of D-tryptophan, L-N-methyltryptophan, L-homophenylalanine, L-2-naphthyl L-tetrahydroisoquinoline, L-cyclohexylalanine, D-leucine, L-fluorenylalanine, or L-histidine;F is the side chain of L-arginine, L-homoarginine, L-citrulline, or L-canavanine; andX is --(CH₂)_nNH-- or (CH₂)_n--S--, where n is an integer of from 1 to 4; --(CH₂)_2O--; --(CH₂)_3O--; --(CH₂)_3--; --(CH₂)_4--; --CH_2COCHRNH--; or --CH_2CHCOCHRNH--, where R is the side chain of any common or uncommon amino acid.

2-23. (canceled)

24. The method of claim 1, in which n is 2 or 3.

25. The method of claim 1, in which A is an acetamide group, an aminomethyl group, or a substituted or unsubstituted sulphonamide group.

26. The method of claim 1, in which A is a substituted sulphonamide, and the substituent is an alkyl chain of 1 to 6 carbon atoms, or a phenyl or toluoyl group.

27. The method of claim 26, in which the substituent is an alkyl chain of 1 to 4 carbon atoms.

28. The method of claim 1, in which B is the side chain of L-phenylalanine or L-phenylglycine.

29. The method of claim 1, in which C is the side chain of glycine, alanine, leucine, valine, proline, hydroxyproline, or thioproline.

30. The method of claim 1, in which D is the side chain of D-Leucine, D-homoleucine, D-cyclohexylalanine, D-homocyclohexylalanine, D-valine, D-norleucine, D-homonorleucine, D-phenylalanine, D-tetrahydroisoquinoline, D-glutamine, D-glutamate, or D-tyrosine.

31. The method of claim 1, in which E is the side chain of an amino acid selected from the group consisting of L-phenylalanine, L-tryptophan and L-homotryptophan, or is L-1-napthyl or L-3-benzothienyl alanine.

32. The method of claim 1, wherein said inhibitor has potent antagonist activity at sub-micromolar concentrations.

33. The method of claim 1, wherein said compound has a receptor affinity IC₅₀<25 μM, and an antagonist potency IC₅₀<1 μM.

34. The method of claim 1, wherein said compound is selected from the group consisting of:AcF-[OPdChaWR] (PMX53), ##STR00003## ##STR00004## ##STR00005## ##STR00006## ##STR00007## ##STR00008## ##STR00009## ##STR00010## ##STR00011## ##STR00012## ##STR00013## ##STR00014## ##STR00015## ##STR00016## ##STR00017## ##STR00018## ##STR00019## ##STR00020## ##STR00021## ##STR00022##

35. The method of claim 1, wherein said compound is AcF-[OPdChaWR] (PMX53).

36. The method of claim 1, wherein said inhibitor is used in conjunction with one or more other agents for the treatment of inflammatory bowel disease.

37. The method of claim 36, wherein said other agent is infliximab or is an inhibitor of C3a.

38. The method of claim 1, wherein said inflammatory bowel disease is ulcerative colitis.

39. The method of claim 1, wherein said inflammatory bowel disease is Crohn's disease.

40. The method of claim 1, wherein said inhibitor is administered in an enteric coated capsule or per-rectally.

41. A method of treating or ameliorating the symptoms of an inflammatory bowel disease in a mammal, said method comprising the step of administering to a mammal in need thereof, an amount of a compound of the formula (AcF-[OPdChaWR]) effective to treat or ameliorate the symptoms of said disease in said mammal.

42. A method of ameliorating one or more symptoms of an inflammatory bowel disease in a mammal, said method comprising the step of administering to a mammal in need thereof, an amount of a C5a receptor antagonist compound effective to ameliorate said one or more symptoms of said inflammatory bowel disease in said mammal, wherein said compound comprises a cyclic peptide or peptidomimetic compound of formula I: ##STR00023## where A is H, alkyl, aryl, NH₂, NH-alkyl, N(alkyl)₂, NH-aryl, NH-acyl, NH-benzoyl, NHSO₃, NHSO_2-alkyl, NHSO_2-aryl, OH, O-alkyl, or O-aryl;B is an alkyl, aryl, phenyl, benzyl, naphthyl or indole group, or the side chain of a D- or L-amino acid, but is not the side chain of glycine, D-phenylalanine, L-homophenylalanine, L-tryptophan, L-homotryptophan, L-tyrosine, or L-homotyrosine;C is the side chain of a D-, L- or homo-amino acid, but is not the side chain of isoleucine, phenylalanine, or cyclohexylalanine;D is the side chain of a neutral D-amino acid, but is not the side chain of glycine or D-alanine, a bulky planar side chain, or a bulky charged side chain;E is a bulky substituent, but is not the side chain of D-tryptophan, L-N-methyltryptophan, L-homophenylalanine, L-2-naphthyl L-tetrahydroisoquinoline, L-cyclohexylalanine, D-leucine, L-fluorenylalanine, or L-histidine;F is the side chain of L-arginine, L-homoarginine, L-citrulline, or L-canavanine; andX is --(CH₂)_nNH-- or (CH₂)_n--S--, where n is an integer of from 1 to 4; --(CH₂)_2O--; --(CH₂)_3O--; --(CH₂)_3--; --(CH₂)_4--; --CH_2COCHRNH--; or --CH_2CHCOCHRNH--, where R is the side chain of any common or uncommon amino acid.

43. A method of treating an inflammatory bowel disease in a mammal, said method comprising the step of administering to a mammal in need thereof, an amount of a C5a receptor antagonist compound effective to treat said inflammatory bowel disease in said mammal, wherein said compound comprises a cyclic peptide or peptidomimetic compound of formula I: ##STR00024## where A is H, alkyl, aryl, NH₂, NH-alkyl, N(alkyl)₂, NH-aryl, NH-acyl, NH-benzoyl, NHSO₃, NHSO_2-alkyl, NHSO_2-aryl, OH, O-alkyl, or O-aryl;B is an alkyl, aryl, phenyl, benzyl, naphthyl or indole group, or the side chain of a D- or L-amino acid, but is not the side chain of glycine, D-phenylalanine, L-homophenylalanine, L-tryptophan, L-homotryptophan, L-tyrosine, or L-homotyrosine;C is the side chain of a D-, L- or homo-amino acid, but is not the side chain of isoleucine, phenylalanine, or cyclohexylalanine;D is the side chain of a neutral D-amino acid, but is not the side chain of glycine or D-alanine, a bulky planar side chain, or a bulky charged side chain;E is a bulky substituent, but is not the side chain of D-tryptophan, L-N-methyltryptophan, L-homophenylalanine, L-2-naphthyl L-tetrahydroisoquinoline, L-cyclohexylalanine, D-leucine, L-fluorenylalanine, or L-histidine;F is the side chain of L-arginine, L-homoarginine, L-citrulline, or L-canavanine; andX is --(CH₂)_nNH-- or (CH₂)_n--S--, where n is an integer of from 1 to 4; --(CH₂)_2O--; --(CH₂)_3O--; --(CH₂)_3--; --(CH₂)_4--; --CH_2COCHRNH--; or --CH_2CHCOCHRNH--, where R is the side chain of any common or uncommon amino acid.

44. The method of claim 42 or claim 43, wherein said compound is selected from the group consisting of:AcF-[OPdChaWR], ##STR00025## ##STR00026## ##STR00027## ##STR00028## ##STR00029## ##STR00030## ##STR00031## ##STR00032## ##STR00033## ##STR00034## ##STR00035## ##STR00036## ##STR00037## ##STR00038## ##STR00039## ##STR00040## ##STR00041## ##STR00042## ##STR00043## ##STR00044##

45. A method of treating or ameliorating the symptoms of ulcerative colitis or Crohn's disease in a mammal, said method comprising the step of administering to a mammal in need thereof, an amount of a compound selected from the group consisting of:(AcF-[OPdChaWR]), ##STR00045## ##STR00046## ##STR00047## ##STR00048## ##STR00049## ##STR00050## ##STR00051## ##STR00052## ##STR00053## ##STR00054## ##STR00055## ##STR00056## ##STR00057## ##STR00058## ##STR00059## ##STR00060## ##STR00061## ##STR00062## ##STR00063## ##STR00064## effective to treat or ameliorate the symptoms of said ulcerative colitis or Crohn's disease in said mammal.