carbenoxolone has been researched along with Diabetes-Mellitus--Type-2* in 3 studies
3 other study(ies) available for carbenoxolone and Diabetes-Mellitus--Type-2
| Article | Year |
|---|---|
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 |
Synthesis and evaluation of piperidine urea derivatives as efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitors in diabetic ob/ob mice.
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has attracted considerable attention as a potential target for the treatment of diabetes and metabolic syndrome. Herein we report the design, synthesis and efficacy evaluation of novel amide and urea 11β-HSD1 inhibitors. Structure-activity relationship studies led to the identification of 10c, which was efficacious in a diabetic ob/ob mouse model and reduced fasting and non-fasting blood glucose levels after ip dosing. Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Animals; Diabetes Mellitus, Type 2; Enzyme Activation; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Mice; Mice, Obese; Molecular Structure; Piperidines; Structure-Activity Relationship; Urea | 2012 |
4-(Phenylsulfonamidomethyl)benzamides as potent and selective inhibitors of the 11beta-hydroxysteroid dehydrogenase type 1 with efficacy in diabetic ob/ob mice.
Selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) have considerable potential as treatments for type 2 diabetes. Presented herein are the syntheses, structure-activity relationships, and efficacy evaluation of 4-(phenylsulfonamidomethyl)benzamides as 11beta-HSD1 inhibitors. Through modification of our initial lead 5, we have identified potent and selective 11beta-HSD1 inhibitors, such as 11n, which demonstrated improved glycemic control, decreased serum lipids, and enhanced insulin sensitivity when dosed ip in diabetic ob/ob mice. Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Animals; Benzamides; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Discovery; Humans; Hydrolysis; Inhibitory Concentration 50; Mice; Mice, Obese; Models, Chemical; Structure-Activity Relationship; Sulfonamides | 2009 |