Use of ribofuranose derivatives against inflammatory bowel diseases

Abstract

A method for the prophylaxis or treatment of an inflammatory bowel disease is provided, comprising administering to a patient having or at risk of developing an inflammatory bowel disease a therapeutically or preventatively effective amount of one or more ribofuranose derivatives having the Formula (I): wherein R is a group selected from a carboxamide, an amidine, and pharmaceutically acceptable acid addition salts thereof, and the configuration at the C 2 carbon of the ribofuranose moiety is D or L. The one or more ribofuranose derivatives (I) may be used in combination with further active agents such as antivirals or agents effective against inflammatory bowel disease.

1 - 42 . (Cancelled)  
     
     
         43 . A medicament for administration against an inflammatory bowel disease, comprising: 
 at least one ribofuranose derivative having the Formula (I):                          in an amount effective to treat or prevent said inflammatory bowel disease in a mammal, wherein R is a group selected from the group consisting of a carboxamide, an amidine and pharmaceutically acceptable acid addition salts thereof and the configuration at the C 2  carbon of the ribofuranose moiety is D or L.    
     
     
         44 . The medicament of  claim 43 , comprising said ribofuranose derivative having Formula (I) in an amount between about 100 mg and 1.5 grams.  
     
     
         45 . The medicament of  claim 44 , wherein said medicament is formulated for oral administration.  
     
     
         46 . The medicament of  claim 43 , wherein said medicament is formulated for intravenous administration, parenteral administration, oral administration, inhalation, topical administration, transdermal administration, rectal administration, continuous infusion, or administration with an osmotic pump or a sustained release implant.  
     
     
         47 . The medicament of  claim 43 , wherein the ribofuranose derivative having Formula (I) comprises at least one riboftiranose derivative selected from the group consisting of 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide, 1-β-L-ribofuranosylH-1,2,4-triazole-3-carboxamide, 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-amidine, 1-β-L-ribofuranosyl-1H-1,2,4-triazole-3-amidine, and pharmaceutically acceptable acid addition salts thereof.  
     
     
         48 . The medicament of  claim 47 , wherein the ribofuranose derivative having Formula (I) is 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide.  
     
     
         49 . The medicament of  claim 43 , wherein the ribofuranose derivative having Formula (I) is 1-β-L-ribofuranosylH-1,2,4-triazole-3-carboxamide.  
     
     
         50 . The medicament of  claim 43 , wherein the ribofuranose derivative having Formula (I) is 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-amidine.  
     
     
         51 . The medicament of  claim 43 , wherein the ribofuranose derivative having Formula (I) is 1-β-L-ribofuranosyl-1H-1,2,4-triazole-3-amidine.  
     
     
         52 . The medicament of  claim 43 , wherein the ribofuranose derivative is the hydrochloric acid addition salt of 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-amidine.  
     
     
         53 . The medicament of  claim 43 , wherein the ribofuranose derivative is the hydrochloric acid addition salt of 1-β-L-ribofuranosyl-1H-1,2,4-triazole-3-amidine.  
     
     
         54 . The medicament of  claim 43 , wherein the ribofuranose derivative having Formula (I) is 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide and said inflammatory bowel disease is Crohn's disease.  
     
     
         55 . The medicament of  claim 54 , wherein said Crohn's disease is selected from the group consisting of active Crohn's disease, refractory Crohn's disease, and fistulizing Crohn's disease.  
     
     
         56 . The medicament of  claim 54 , comprising said ribofuranose derivative having Formula (I) in an amount between about 100 mg and 1.5 grams.  
     
     
         57 . The medicament of  claim 56 , wherein said medicament is formulated for oral administration.  
     
     
         58 . The medicament of  claim 43 , further comprising one or more antivirals for administration simultaneously in admixture, separately and simultaneously, or separately in any order with said derivative having the Formula (I).  
     
     
         59 . The medicament of  claim 43  or  58 , further comprising one or more further agents effective against an inflammatory bowel disease for administration simultaneously in admixture, separately and simultaneously, or separately in any order with said derivative having the Formula (I), wherein the further agent is selected the group consisting of anti-inflammatories, immunosuppressants, antibodies, antibody fragments, humanized monoclonal antibody against TNF-α, flavonoids, monoclonal antibodies against IL-12, monoclonal antibodies against IL-6, monoclonal antibodies against the α4β7 integrin receptor, keratinocyte growth factor, protein inhibitors of TNF-α, glucocorticoids, peptide analogues of glucagon-like peptide-2, glutathione peroxidase mimics, anti-sense TNF inhibitors, anti-sense ICAM-1 inhibitor, nitric oxide-releasing steroid derivatives, analogues of GLP-2, neurokinin-1 antagonists, NF-kappa-B inhibitors, orally-active phosphodiesterase IV inhibitors, thiazole derivatives, 5-lipoxygenase inhibitors, L-selectin antagonists, enzyme inhibitors, tryptase inhibitors, immunosuppressive macrolides, monoclonal antibodies against the α4β7 integrin receptor, glutathione peroxidase mimics, interferon, omega-3 fatty acids, inhibitors of cytokine synthesis, bactericidal/permeability agents , guanyl-hydrazone compounds, apoptotic antineoplastic drugs, thalidomide, recombinant interleukin-11 and mixtures thereof.  
     
     
         60 . The medicament of  claim 59 , wherein the further agent is in an amount that is from about half the dosage to the same dosage which, when the further agent is administered alone, is effective to treat or prevent said inflammatory bowel disease.  
     
     
         61 . The medicament of  claim 58 , wherein said antiviral is selected from the group consisting of abacavir, acyclovir, acyclovir sodium, acyclovir potassium, adefovir, amantadine, amprenavir, atazanavir, brivudine, capravirine, cidofovir, delavirdine, didanosine, efavirenz, emivirin, emtricitabine, enfurvirtide, famciclovir, fiacitabine, fialuridine, fosamprenavir, foscamet, ganciclovir, idoxuridine, indinavir, lamivudine, lobucavir, lopinavir, memantine, mozenavir, nelfinavir, netuvidine, nevirapine, oseltamivir, penciclovir, rimantidine, pentafuside, ritonavir, saquinavir, sorivudine, stavudine, tenofovir, tipranavir, trifluridine, vidarabine, valaciclovir, valganciclovir, zalcitabine, zanamivir, zidovudin, and the pharmaceutically acceptable salts thereof and mixtures thereof.  
     
     
         62 . The medicament of  claim 58 , wherein the ribofuranose derivatives are 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide and 1-β-L-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide and the antiviral is acyclovir.  
     
     
         63 . The medicament of  claim 43 , wherein the disease is selected from the group consisting of pseudomembranous colitis, hemorrhagic colitis, hemolytic-uremic syndrome colitis, collagenous colitis, ischemic colitis, radiation colitis, drug and chemically induced colitis, diversion colitis, ulcerative colitis, irritable bowel syndrome, irritable colon syndrome and Crohn's disease.