Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension

  • Bioorg Med Chem Lett. 2013 Jun 15;23(12):3650-3. doi: 10.1016/j.bmcl.2013.03.011.
David R Bauman  1 ,  Alan Whitehead ,  Lisa C Contino ,  Jisong Cui ,  Margarita Garcia-Calvo ,  Xin Gu ,  Nancy Kevin ,  Xiuying Ma ,  Lee-yuh Pai ,  Kashmira Shah ,  Xiaolan Shen ,  Sloan Stribling ,  Hratch J Zokian ,  Joe Metzger ,  Diane E Shevell ,  Sherman T Waddell
Affiliations
  • 1. Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
Abstract

In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11β-HSD1 inhibitors, we examined a set of 11β-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11β-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11β-HSD1 independent pathway.

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