Literature DB >> 25050169

Optimization of 1,2,4-Triazolopyridines as Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1).

Jun Li1, Lawrence J Kennedy1, Haixia Wang1, James J Li1, Steven J Walker1, Zhenqiu Hong1, Stephen P O'Connor1, Akbar Nayeem1, Daniel M Camac2, Paul E Morin2, Steven Sheriff2, Mengmeng Wang1, Timothy Harper1, Rajasree Golla1, Ramakrishna Seethala1, Thomas Harrity1, Randolph P Ponticiello1, Nathan N Morgan1, Joseph R Taylor1, Rachel Zebo1, David A Gordon1, Jeffrey A Robl1.   

Abstract

Small alkyl groups and spirocyclic-aromatic rings directly attached to the left side and right side of the 1,2,4-triazolopyridines (TZP), respectively, were found to be potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase-type 1 (11β-HSD-1) enzyme. 3-(1-(4-Chlorophenyl)cyclopropyl)-8-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridine (9f) was identified as a potent inhibitor of the 11β-HSD-1 enzyme with reduced Pregnane-X receptor (PXR) transactivation activity. The binding orientation of this TZP series was revealed by X-ray crystallography structure studies.

Entities:  

Keywords:  Enzyme inhibitors; human 11β-hydroxysteroid dehydrogenase-type 1; triazolopyridines

Year:  2014        PMID： 25050169      PMCID： PMC4094253          DOI： 10.1021/ml500144h

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


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