2. Academic Validation
  3. Bicyclo[2.2.2]octyltriazole inhibitors of 11β-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome

Bicyclo[2.2.2]octyltriazole inhibitors of 11β-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome

  • Bioorg Med Chem Lett. 2011 Apr 15;21(8):2568-72. doi: 10.1016/j.bmcl.2011.01.018.
Milana Maletic 1,  Aaron Leeman,  Michael Szymonifka,  Steven S Mundt,  Hratch J Zokian,  Kashmira Shah,  Jasminka Dragovic,  Kathy Lyons,  Rolf Thieringer,  Anne H Vosatka,  James Balkovec,  Sherman T Waddell
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. milana_maletic@merck.com
PMID: 21421311 DOI: 10.1016/j.bmcl.2011.01.018
Abstract

Following the discovery of a metabolic 'soft-spot' on a bicyclo[2.2.2]octyltriazole lead, an extensive effort was undertaken to block the oxidative metabolism and improve PK of this potent HSD1 lead. In this communication, SAR survey focusing on various alkyl chain replacements will be detailed. This effort culminated in the discovery of a potent ethyl sulfone inhibitor with an improved PK profile across species and improved physical properties.

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