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Piperazine Sulfonamides as Potent, Selective, and Orally Available 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors with Efficacy in the Rat Cortisone-Induced Hyperinsulinemia Model
- Source :
- Journal of Medicinal Chemistry. 51:4068-4071
- Publication Year :
- 2008
- Publisher :
- American Chemical Society (ACS), 2008.
-
Abstract
- 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is the enzyme that converts cortisone to cortisol. Evidence suggests that selective inhibition of 11beta-HSD1 could treat diabetes and metabolic syndrome. Presented herein are the synthesis, structure-activity relationship, and in vivo evaluation of piperazine sulfonamides as 11beta-HSD1 inhibitors. Through modification of our initial lead 5a, we have identified potent and selective 11beta-HSD1 inhibitors such as 13q and 13u with good pharmacokinetic properties.
- Subjects :
- medicine.medical_specialty
Administration, Oral
Biological Availability
Dehydrogenase
Piperazines
chemistry.chemical_compound
In vivo
11β-hydroxysteroid dehydrogenase type 1
Hyperinsulinism
Internal medicine
11-beta-Hydroxysteroid Dehydrogenase Type 1
Drug Discovery
medicine
Hyperinsulinemia
Animals
Enzyme Inhibitors
chemistry.chemical_classification
Sulfonamides
biology
Sulfonamide (medicine)
medicine.disease
Rats
Cortisone
Disease Models, Animal
Piperazine
Enzyme
Endocrinology
chemistry
biology.protein
Molecular Medicine
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....5a7aa456ea0bed0ab0f466405eab7742