Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid receptor modulator-statin hybrids.

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Link JT, Sorensen BK, Lai C, Wang J, Fung S, Deng D, Emery M, Carroll S, Grynfarb M, Goos-Nilsson A, Von Geldern T

Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid receptor modulator-statin hybrids.

Bioorg Med Chem Lett. 2004 Aug 16;14(16):4173-8.

PubMed ID

15261265 [ View in PubMed

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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 IC(50)=7 nM) and nonsteroidal modulator hybrids like 16 (h-GR binding IC(50)=2 nM) were discovered. Appending a 'statin'-like diol-acid group to the modulators dramatically improved metabolic stability (and in some cases hepatocyte activity), but did not impart hepatoselectivity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mifepristone	Glucocorticoid receptor	IC 50 (nM)	1.1	N/A	N/A	Details
Mifepristone	Glucocorticoid receptor	IC 50 (nM)	4.8	N/A	N/A	Details
Mifepristone	Progesterone receptor	IC 50 (nM)	2.9	N/A	N/A	Details