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Bioorg Med Chem Lett. 2011 Apr 15;21(8):2568-72. doi: 10.1016/j.bmcl.2011.01.018. Epub 2011 Jan 11.

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

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. milana_maletic@merck.com

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.

PMID:
21421311
DOI:
10.1016/j.bmcl.2011.01.018
[Indexed for MEDLINE]

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