954232-87-2Relevant academic research and scientific papers
Optimisation of pharmacokinetic properties in a neutral series of 11β-HSD1 inhibitors
Scott, James S.,Gill, Adrian L.,Godfrey, Linda,Groombridge, Sam D.,Rees, Amanda,Revill, John,Schofield, Paul,S?rme, Pernilla,Stocker, Andrew,Swales, John G.,Whittamore, Paul R.O.
, p. 6756 - 6761 (2013/01/14)
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.
SUBSTITUTED PYRIMIDIN-5-CARBOXAMIDES 281
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Page/Page column 36, (2009/10/30)
A compound of formula (I): and pharmaceutically-acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11betaHSD1, processes for making them and pharmaceutical compositions comprising them are also described.
