Adamantyl carboxamides and acetamides as potent human 11β-hydroxysteroid dehydrogenase type 1 inhibitors

Graphical abstract Series of adamantyl carboxamide and acetamide derivatives were identified, providing potent and selective inhibitors of the therapeutic target human 11β-hydroxysteroid dehydrogenase type 1.

[1]  R. Gregg,et al.  Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1. , 2010, Bioorganic & medicinal chemistry letters.

[2]  A. Odermatt,et al.  A rapid screening assay for inhibitors of 11β-hydroxysteroid dehydrogenases (11β-HSD): flavanone selectively inhibits 11β-HSD1 reductase activity , 2003, Molecular and Cellular Endocrinology.

[3]  B. Walker,et al.  Printed in U.S.A. Copyright © 2001 by The Endocrine Society Minireview: 11�-Hydroxysteroid Dehydrogenase Type 1— A Tissue-Specific Amplifier of Glucocorticoid Action* , 2000 .

[4]  B. Potter,et al.  Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery. , 2011, Future medicinal chemistry.

[5]  Mark P Thomas,et al.  Adamantyl Ethanone Pyridyl Derivatives: Potent and Selective Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1 , 2011, ChemMedChem.

[6]  R. Ge,et al.  11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors as Promising Therapeutic Drugs for Diabetes: Status and Development , 2010 .

[7]  B. Potter,et al.  Discovery of Adamantyl Ethanone Derivatives as Potent 11β‐Hydroxysteroid Dehydrogenase Type 1 (11β‐HSD1) Inhibitors , 2010, ChemMedChem.

[8]  T. Kowalski,et al.  11β-hydroxysteroid dehydrogenase type 1 inhibitors: a review of recent patents , 2009, Expert opinion on therapeutic patents.

[9]  Mark P Thomas,et al.  Synthesis and evaluation of thiadiazole derivatives as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 , 2012 .

[10]  Richard Barnett Diabetes , 1904, The Lancet.

[11]  J. Flier,et al.  Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. , 2003, The Journal of clinical investigation.

[12]  J. Seckl,et al.  Local Amplification of Glucocorticoids by 11β‐Hydroxysteroid Dehydrogenase Type 1 and Its Role in the Inflammatory Response , 2006, Annals of the New York Academy of Sciences.

[13]  R. Thieringer,et al.  11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice , 2005, The Journal of experimental medicine.

[14]  K. Svenson,et al.  Efficacious 11beta-hydroxysteroid dehydrogenase type I inhibitors in the diet-induced obesity mouse model. , 2009, Journal of medicinal chemistry.

[15]  J. Flier,et al.  Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. , 2004, Diabetes.

[16]  J. Rosenstock,et al.  The 11-β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor INCB13739 Improves Hyperglycemia in Patients With Type 2 Diabetes Inadequately Controlled by Metformin Monotherapy , 2010, Diabetes Care.

[17]  K. Longenecker,et al.  Adamantane sulfone and sulfonamide 11-β-HSD1 Inhibitors , 2007 .

[18]  T. Mune,et al.  NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning and characterization of cDNA from sheep kidney. , 1994, The Journal of biological chemistry.

[19]  E. Valeur,et al.  Discovery and structure-activity relationships of pentanedioic acid diamides as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type I. , 2009, Bioorganic & medicinal chemistry letters.

[20]  Edwards,et al.  11 b-Hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress , 1997 .

[21]  Warszawski Uniwersytet Medyczny,et al.  Diabetes care , 2019, Health at a Glance.

[22]  H. Tutill,et al.  Novel inhibitors of 17beta-hydroxysteroid dehydrogenase type 1: templates for design. , 2008, Bioorganic & medicinal chemistry.

[23]  B. Potter,et al.  Discovery of novel inhibitors of human 11β-hydroxysteroid dehydrogenase type 1 , 2009, Molecular and Cellular Endocrinology.

[24]  R. Thieringer,et al.  Inhibition of 11β-HSD1 as a novel treatment for the metabolic syndrome: do glucocorticoids play a role? , 2005, Expert review of cardiovascular therapy.

[25]  Minghan Wang,et al.  Nutrition & Metabolism BioMed Central Review The role of glucocorticoid action in the pathophysiology of the Metabolic Syndrome , 2004 .

[26]  C. Kim,et al.  Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group. , 2011, Bioorganic & medicinal chemistry letters.

[27]  Mark P Thomas,et al.  Discovery of Adamantyl Heterocyclic Ketones as Potent 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors , 2011, ChemMedChem.

[28]  Minghan Wang,et al.  Blockade of glucocorticoid excess at the tissue level: inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 as a therapy for type 2 diabetes. , 2008, Journal of medicinal chemistry.

[29]  Jiandong Zhang,et al.  Discovery of a potent, orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: identification of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). , 2010, Journal of medicinal chemistry.

[30]  B. Walker,et al.  Pathophysiology of modulation of local glucocorticoid levels by 11β-hydroxysteroid dehydrogenases , 2001, Trends in Endocrinology & Metabolism.

[31]  John J. Mullins,et al.  Improved Lipid and Lipoprotein Profile, Hepatic Insulin Sensitivity, and Glucose Tolerance in 11β-Hydroxysteroid Dehydrogenase Type 1 Null Mice* , 2001, The Journal of Biological Chemistry.

[32]  J. Flier,et al.  Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity. , 2005, Diabetes.

[33]  Jeremy W Tomlinson,et al.  11 (cid:1) -Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response , 2004 .