Methods for treating autoimmune disorders, and reagents related thereto

• US 8,410,053 B2
• Filed: 11/26/2002
• Issued: 04/02/2013
• Est. Priority Date: 11/26/2001
• Status: Expired due to Fees

• Current Assignee: Brigham and Women's Hospital Incorporated, Trustees of Tufts College
• Original Assignee: Brigham and Women's Hospital Incorporated, Trustees of Tufts College
• Inventors: Bachovchin, William W., Kuchroo, Vijay K.
• Primary Examiner(s): HEARD, THOMAS SWEENEY
• Application Number:
  US10/496,627
• Publication Number:
  US 20050070459A1
• Time in Patent Office: 3,780 Days
• Field of Search: None
• US Class Current: 514/17.9
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 38/005 Enzyme inhibitors protease inhibitors A61K38/55
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid

Abstract

The invention generally relates to improved methods for treatment or prophylaxis in animal subjects (including humans) of autoimmune disorders including Type I diabetes, septic shock, multiple sclerosis, inflammatory bowel disease (IBD) and Crohn'"'"'s disease.

Claims

1. A method for treating an autoimmune disease in an animal, comprising administering to said animal a composition comprising one or more inhibitors of DPIV in an amount sufficient to suppress the immune system to treat said autoimmune disease, wherein said autoimmune disease is selected from the group consisting of multiple sclerosis, systemic lupus erythematosus (SLE), myasthenia gravis, Grave'"'"'s disease, and type II collagen-induced arthritis;

and said inhibitor of DPIV is represented by the formula;

2. The method of claim 1, wherein the autoimmune disease is multiple sclerosis.

R₃₆ is lower alkyl and R₃₈ is hydrogen, or, R₃₆ and R₃₈ together form a 4-7 membered heterocycle;

and

R₄₀ represents a C-terminally linked naturally-occurring α

-amino acid residue selected from the group consisting of glycine, alanine, valine, cysteine, leucine, isoleucine, serine, threonine, methionine, glutamic acid, aspartic acid, glutamine, asparagine, lysine, arginine, proline, histidine, phenylalanine, tyrosine, and tryptophan.

3. The method of claim 1, wherein the inhibitor is orally active.

4. The method of claim 1, wherein

6. The method of claim 1, wherein R₁ represents lower alkyl.

7. The method of claim 1, wherein R₁ represents methyl.

8. The method of claim 1, wherein R₂ is t-butyl or cyclohexyl.

9. The method of claim 1, wherein:

R₁ represents methyl;

R₂ represents cyclohexyl; and

R₃ and R₄ represent, independently and for each occurrence, hydrogen.

10. The method of claim 1, wherein the inhibitor is represented by the formula:

11. The method of claim 10, wherein:

W represents

5. A method for treating an autoimmune disease in an animal, comprising administering to said animal a composition comprising one or more inhibitors of DPIV in an amount sufficient to suppress the immune system to treat said autoimmune disease, wherein said autoimmune disease is selected from the group consisting of multiple sclerosis, systemic lupus erythematosus (SLE), myasthenia gravis, Grave'"'"'s disease, and type II collagen-induced arthritis;

and said inhibitor of DPIV is represented by the formula;