Discovery of potent, nonsteroidal, and highly selective glucocorticoid receptor antagonists.

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Morgan BP, Swick AG, Hargrove DM, LaFlamme JA, Moynihan MS, Carroll RS, Martin KA, Lee E, Decosta D, Bordner J

Discovery of potent, nonsteroidal, and highly selective glucocorticoid receptor antagonists.

J Med Chem. 2002 Jun 6;45(12):2417-24.

PubMed ID

12036351 [ View in PubMed

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Abstract

An approach to the computer-assisted, pharmacophore design of nonsteroidal templates for the glucocorticoid receptor (GR) that contained an element of pseudo-C2 symmetry was developed. The enatiomer of the initial design, 1Ra, and not the designed molecule, 1S, showed the desired ligand binding to the GR. The pseudo-C2 symmetry of the template allowed for rapid improvements in GR activity resulting in potent, selective, nonsteroidal GR antagonists, CP-394531 and CP-409069.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mifepristone	Glucocorticoid receptor	Ki (nM)	0.24	N/A	N/A	Details
Mifepristone	Progesterone receptor	Ki (nM)	15	N/A	N/A	Details