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Synthesis of sterically encumbered 11β-aminoprogesterone derivatives and evaluation as 11β-hydroxysteroid dehydrogenase inhibitors and mineralocorticoid receptor antagonists

Pandya, Keyur and Dietrich, David and Seibert, Julia and Vederas, John C. and Odermatt, Alex. (2013) Synthesis of sterically encumbered 11β-aminoprogesterone derivatives and evaluation as 11β-hydroxysteroid dehydrogenase inhibitors and mineralocorticoid receptor antagonists. Bioorganic & medicinal chemistry letters, Vol. 21, H. 21. pp. 6274-6281.

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Official URL: http://edoc.unibas.ch/dok/A6194600

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Abstract

11β-Hydroxyprogesterone is a well-known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2. It also activates the mineralocorticoid receptor (MR). Modulation of corticosteroid action by inhibition of 11βHSDs or blocking MR is currently under consideration for treatment of electrolyte disturbances, metabolic diseases and chronic inflammatory disorders. We established conditions to synthesize sterically demanding 11β-aminoprogesterone, which following subsequent nucleophilic or reductive amination, allowed extension of the amino group to prepare amino acid derivatives. Biological testing revealed that some of the 11β-aminoprogesterone derivatives selectively inhibit 11βHSD2. Moreover, two compounds that did not significantly inhibit 11βHSDs had antagonist properties on MR. The 11β-aminoprogesterone derivatives form a basis for the further development of improved modulators of corticosteroid action.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex and Seibert, Julia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Pergamon
ISSN:0960-894X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Dec 2013 09:35
Deposited On:06 Dec 2013 09:35

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