title: Synthesis and biological analysis of benzazol-2-yl piperazine sulfonamides as 11β-hydroxysteroid dehydrogenase 1 inhibitors.
abstract: In the last decade the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) emerged as a promising new strategy to treat diabetes and several metabolic syndrome phenotypes. Using a molecular modeling approach and classical bioisosteric studies, we discovered a new class of 11β-HSD1 inhibitors bearing an arylsulfonylpiperazine scaffold. Optimization of the initial lead resulted in compound 11 that selectively inhibits 11β-HSD1 (IC50=0.7 μM).
authors: Institute of Pharmacy, Department of Pharmaceutical Chemistry, Leopold-Franzens-Universität, Centrum für Chemie und Biomedizin, Innsbruck, Austria.
authors: Sandra
authors: S
authors: Hofer
authors: Denise V
authors: DV
authors: Kratschmar
authors: Brigitte
authors: B
authors: Schernthanner
authors: Anna
authors: A
authors: Vuorinen
authors: Daniela
authors: D
authors: Schuster
authors: Alex
authors: A
authors: Odermatt
authors: Johnny
authors: J
authors: Easmon
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D001393:Azoles / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001393:Azoles; D004791:Enzyme Inhibitors; D010879:Piperazines; D013449:Sulfonamides; D000077489:Piperazine; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1
keywords: 11β-Hydroxysteroid dehydrogenase; 2-Benzazolylpiperazine; Metabolic diseases; Molecular modeling; Structure–activity relationships (SAR)