Title of article :
Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid receptor modulator–statin hybrids
Author/Authors :
J.T Link، نويسنده , , Bryan K. Sorensen، نويسنده , , Chunqiu Lai، نويسنده , , Jiahong Wang، نويسنده , , Steven Fung، نويسنده , , Daisy Deng، نويسنده , , Maurice Emery، نويسنده , , Sherry Carroll، نويسنده , , Marlena Grynfarb، نويسنده , , Annika Goos-Nilsson، نويسنده , , Thomas von Geldern، نويسنده ,
Abstract :
The synthesis, activity, metabolic stability, and pharmacokinetics of steroidal and nonsteroidal glucocorticoid receptor modulator–statin hybrids is reported. Potent steroidal antagonist–statin hybrids like 22 (h-GR binding IC50=7 nM) and nonsteroidal modulator hybrids like 16 (h-GR binding IC50=2 nM) were discovered. Appending a `statinʹ-like diol-acid group to the modulators dramatically improved metabolic stability (and in some cases hepatocyte activity), but did not impart hepatoselectivity.
Keywords :
Statin.* Corresponding author. Tel.: +1-847-935-6806 , fax: +1-847-938-1674 , e-mail: james.link@abbott.com , Glucocorticoid receptor modulator
