Corticotropin Releasing Factor Receptor Antagonists

What is this patent about?

’557 is related to the field of pharmaceutical compositions and methods for treating congenital adrenal hyperplasia (CAH). CAH results from enzyme deficiencies that disrupt hormone production in the adrenal gland, leading to excess androgen production and insufficient glucocorticoid and mineralocorticoid synthesis. Current treatments involve glucocorticoid replacement therapy, but high doses can lead to adverse side effects. There is a need for alternative treatments that can normalize hormone levels and reduce the reliance on high-dose glucocorticoids.

The underlying idea behind ’557 is to use a CRF1 receptor antagonist to treat CAH. Corticotropin-releasing factor (CRF) stimulates the release of adrenocorticotropic hormone (ACTH), which in turn drives steroidogenesis in the adrenal gland. By blocking the CRF1 receptor, the invention aims to reduce ACTH levels, thereby decreasing the production of excess androgens and normalizing hormone levels in CAH patients. This approach could potentially reduce the need for high doses of glucocorticoids and their associated side effects.

The claims of ’557 focus on a method for treating CAH in a human by administering a therapeutically effective amount of a CRF1 receptor antagonist or a pharmaceutically acceptable salt thereof. The method requires that the administration of the CRF1 receptor antagonist results in a reduction of the adrenocorticotropic hormone (ACTH) level by at least about 10% from baseline, and a reduction of the 17-hydroxyprogesterone (17-OHP) level by at least about 10% from baseline.

In practice, the CRF1 receptor antagonist, specifically 3-(4-Chloro-2-(morpholin-4-yl)thiazol-5-yl)-7-(1-ethylpropyl)-2,5-dimethylpyrazolo(1,5-a)pyrimidine (Compound 1), is formulated into a pharmaceutical composition, such as a capsule or tablet, and administered to a patient with CAH. The dosage is adjusted to achieve a therapeutic effect, which is measured by monitoring hormone levels like ACTH and 17-OHP. The goal is to reduce these hormone levels to a predetermined range, followed by a maintenance therapy of daily dosing of Compound 1.

This approach differs from prior solutions that rely solely on glucocorticoid replacement therapy. By targeting the CRF1 receptor, the invention aims to address the underlying cause of hormone imbalances in CAH, rather than just replacing deficient hormones. This can potentially lead to a more balanced hormonal profile and reduce the need for high doses of glucocorticoids, thereby minimizing the associated side effects and improving the overall quality of life for CAH patients. The reduction in ACTH and 17-OHP are key indicators of the treatment's effectiveness.