Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593505 | Bioorganic & Medicinal Chemistry Letters | 2012 | 6 Pages |
Abstract
11β-HSD1 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. In this program of work we describe how a series of neutral 2-thioalkyl-pyridine 11β-HSD1 inhibitors were optimized in terms of their pharmacokinetic properties to give compounds with excellent bioavailability in both rat and dog through a core change to pyrimidine. A potential reactive metabolite issue with 4-thioalkyl-pyrimidines was circumvented by a switch from sulfur to carbon substitution.
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Authors
James S. Scott, Adrian L. Gill, Linda Godfrey, Sam D. Groombridge, Amanda Rees, John Revill, Paul Schofield, Pernilla Sörme, Andrew Stocker, John G. Swales, Paul R.O. Whittamore,