1257249-91-4Relevant academic research and scientific papers
An in situ oxidation strategy towards overcoming hERG affinity
Pryde, David C.,Jones, Rhys,Middleton, Donald S.,Laverty, Ben J.,Fenwick, David R.,Mason, Helen J.,Corless, Martin,Smith, Nick N.
scheme or table, p. 6400 - 6404 (2010/12/18)
In an effort to overcome hERG affinity with a lead compound, several S-oxide and N-oxide analogues were synthesised with a much improved hERG profile but low in vivo absorption. This led to the implementation of an in situ oxidation strategy wherein a sulfide was dosed orally and systemic levels of the corresponding sulfoxide and sulfone were monitored. SAR and pharmacokinetic data to support this as a possible strategy are presented, although ultimately the approach was shown not to be suitable due to very low levels of active circulating metabolites.
