Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto

Abstract

The present invention relates to certain fused aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. Ser. No. 11 / 355,785, filed Feb. 16, 2006, which is a divisional of U.S. Ser. No. 10 / 890,549, now U.S. Pat. No. 7,132,426, filed Jul. 13,2004, which in turn claims the benefit of U.S. Provisional Applications Ser. Nos. 60 / 487,443, filed Jul. 14, 2003 and 60 / 510,644, filed Oct. 10, 2003, each of which is hereby incorporated by reference in its entirety.FIELD OF THE INVENTION [0002] The present invention relates to certain fused aryl and heteroaryl derivatives that are modulators of glucose metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity. BACKGROUND OF THE INVENTION [0003] Diabetes mellitus is a serious disease afflicting over 100 million people worldwide. In the United States, there are more than 12 million diabetics, with 600,000 new cases diagnosed each year. [0...

AI Technical Summary

Benefits of technology

The compounds effectively modulate the RUP3 receptor to decrease food intake, induce satiety, and control weight gain, providing a safer and more targeted approach to managing metabolic disorders such as diabetes and obesity.

Problems solved by technology

However, people who have diabetes either don't produce insulin or can't efficiently use the insulin they produce; therefore, they can't move glucose into their cells.

Glucose accumulates in the blood creating a condition called hyperglycemia, and over time, can cause serious health problems.

NIDDM is characterized by a relative disparity between endogenous insulin production and insulin requirements, leading to elevated blood glucose levels.

In addition, the onset can be insidious or even clinically inapparent, making diagnosis difficult.

However, after several decades, β cell function deteriorates and non-insulin-dependent diabetes develops in about 20% of the obese population (Pederson, P.

However, the factors which predispose a fraction of patients to alteration of insulin secretion in response to fat accumulation remain unknown.

There are problems with this definition in that it does not take into account the proportion of body mass that is muscle in relation to fat (adipose tissue).

As the BMI increases there is an increased risk of death from a variety of causes that is independent of other risk factors.

Orlistat (a lipase inhibitor) inhibits fat absorption directly and tends to produce a high incidence of unpleasant (though relatively harmless) side-effects such as diarrhea.

However, both products were withdrawn after reports of preliminary evidence of heart valve abnormalities associated with their use.

Obesity considerably increases the risk of developing cardiovascular diseases as well.

Kidney disease, also called nephropathy, occurs when the kidney's “filter mechanism” is damaged and protein leaks into urine in excessive amounts and eventually the kidney fails.

Diabetes is also a leading cause of damage to the retina at the back of the eye and increases risk of cataracts and glaucoma.

Finally, diabetes is associated with nerve damage, especially in the legs and feet, which interferes with the ability to sense pain and contributes to serious infections.

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