3-(1-adamantyl)-6-7-8-9-tetrahydro-5h-(1-2-4)triazolo(4-3-a)azepine has been researched along with Metabolic-Syndrome* in 2 studies
1 review(s) available for 3-(1-adamantyl)-6-7-8-9-tetrahydro-5h-(1-2-4)triazolo(4-3-a)azepine and Metabolic-Syndrome
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Medicinal chemistry of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is the enzyme primarily responsible for the regulation of intracellular cortisol levels. Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. Emerging literature also supports a potential role in the treatment of other unmet medical needs including Alzheimer's disease, vascular inflammation, cardiovascular disease, and glaucoma. The aim of this article is to review the medicinal chemistry literature around small molecule approaches to developing synthetic inhibitors of 11β-HSD1 and to highlight key compounds that have resulted from the efforts of both industrial and academic groups. The reported data from 11β-HSD1 inhibitors that have progressed into the clinic are summarized followed by a perspective from the authors. Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Alzheimer Disease; Animals; Cardiovascular Diseases; Clinical Trials as Topic; Glaucoma; Glucocorticoids; Humans; Metabolic Syndrome | 2014 |
1 other study(ies) available for 3-(1-adamantyl)-6-7-8-9-tetrahydro-5h-(1-2-4)triazolo(4-3-a)azepine and Metabolic-Syndrome
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Discovery of 1'-(1-phenylcyclopropane-carbonyl)-3H-spiro[isobenzofuran-1,3'-pyrrolidin]-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11β-HSD1 using a scaffold-hopping approach.
11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11β-HSD1, particularly in adipose tissues, has been associated with metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11β-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a three-point pharmacophore for 11β-HSD1 that was utilized to design a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of INCB13739. Clinical evaluation of INCB13739 confirmed for the first time that tissue-specific inhibition of 11β-HSD1 in patients with type 2 diabetes mellitus was efficacious in controlling glucose levels and reducing cardiovascular risk factors. Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Humans; Hydrocortisone; Metabolic Syndrome | 2022 |