Genipin derivatives and uses thereof

Abstract

Genipin derivatives and pharmaceutical compositions thereof that inhibit the activity of uncoupling protein-2 (UCP2) and are useful in treating deficient first-phase insulin secretion, non-insulin dependent diabetes mellitus, and ischemia in a mammal are disclosed.

Description

RELATED APPLICATION [0001] This application is a continuation of Application No. PCT / US2004 / 009957 filed on Mar. 31, 2004, which claims the benefit of U.S. Provisional Application No. 60 / 459,278, filed on Mar. 31, 2003, the entire teachings of which are incorporated herein by reference.GOVERNMENT SUPPORT [0002] The invention was supported, in whole or in part, by a grant R01 DK53477 from National Institutes of Health. The Government has certain rights in the invention.BACKGROUND OF THE INVENTION [0003] Diabetes is a disease in which a mammal's ability to regulate glucose levels in the blood is impaired because the mammal has a reduced ability to convert glucose to glycogen for storage in muscle and liver cells. In Type I diabetes, this reduced ability to store glucose is caused by reduced insulin production. Type II diabetes mellitus (also known as non-insulin dependent diabetes) is the form of diabetes which is due to a profound resistance to insulin stimulating or regulatory effec...

AI Technical Summary

Benefits of technology

The present invention is about compounds and pharmaceutical compositions that inhibit the activity of uncoupling protein-2 (UCP2), which is involved in the pathophysiology of various diseases such as deficient first-phase insulin secretion, non-insulin dependent diabetes mellitus, and ischaemic reperfusion disease. The invention provides compounds that directly attack UCP2, reducing its activity and improving the treatment of these diseases. The compounds are derived from genipin, a component of gardenia extract. The invention also includes methods of using these compounds for the treatment of UCP2-related diseases.

Problems solved by technology

However, compliance can be poor and as the disease progresses treatment with hypoglycemics, typically sulfonylureas, thiazolidinediones, or metformin, is often necessary.

However, in many patients, these pharmaceutical agents prove inadequate for maintaining blood glucose at an acceptable level and injection with insulin is necessary.

Since insulin injection has the life threatening side effect of hypoglycemic coma, patients using insulin injections must carefully control dosage.

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