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 C2 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.

Description

BACKGROUND OF INVENTION [0001] 1. Field of the Invention [0002] This invention relates to a method for treatment and prevention of inflammatory bowel disease which comprises administering an effective amount of a ribofuranose derivative or a pharmaceutically acceptable salt thereof to a mammal. This invention further relates to the use of such compounds in the preparation of a medicament for the treatment and prevention of inflammatory bowel disease. BACKGROUND OF THE INVENTION [0003] Inflammatory bowel disease (IBD) is a term used in the art to generically encompass diseases of the intestine such as ulcerative colitis (UC), irritable bowel syndrome, irritable colon syndrome and Crohn's disease (CD). For many of these diseases, in particular CD, the origin of the disease (bacterial, viral or autoimmune) is unknown. There is sufficient overlap in the diagnostic criteria for UC and CD that it is sometimes impossible to say which a given patient has; however, the type of lesion typical...

AI Technical Summary

Benefits of technology

Ribofuranose derivatives demonstrate the ability to induce clinical remission and prevent IBD, potentially reducing the need for surgical interventions and minimizing side effects associated with current therapies, while providing effective management of the disease.

Problems solved by technology

Crohn's disease is currently neither medically nor surgically curable, requiring approaches to treatment that maintains symptomatic control, quality of life, and minimizes short- and long-term toxicity of therapy.

Possible side effects of 5-ASA preparations include nausea, vomiting, heartburn, diarrhea and headaches.

Other treatments have been based on corticosteroids such as cortisone, however prolonged use of steroids has been known to result in side effects such as weight gain, shrinking of the adrenal glands, gray cataract, glaucoma, osteoporosis and diabetes mellitus.

The use of immune modifying drugs such as 6-mercaptopurine and its prodrug azathioprine against Crohn's disease has increased in recent years, but these drugs are slow acting and clinical activity cannot be expected until several weeks or even months of treatment has elapsed.

A drawback of this therapy is the high risk of severe infections when administered by injection and the risk of lymphoproliferative disease.

Unfortunately, CD is characterized by a high rate of recurrence; about 5% of patients need a second surgery each year after initial surgery.

Presumably this is due to the recurrent cycles of injury to the epithelium, followed by regrowth, increasing the risk of transformation.

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