Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist.

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Fuhrmann U, Hess-Stumpp H, Cleve A, Neef G, Schwede W, Hoffmann J, Fritzemeier KH, Chwalisz K

Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist.

J Med Chem. 2000 Dec 28;43(26):5010-6.

PubMed ID

11150172 [ View in PubMed

]

Abstract

Herein we describe the chemical synthesis and pharmacological characterization of a novel, highly potent progesterone receptor (PR) antagonist, ZK 230211. The introduction of a 17alpha-pentafluorethyl side chain in the D-ring of the steroid skeleton allowed the combination of high antiprogestagenic activity with little or no other endocrinological effects. In contrast to many other antiprogestins, ZK 230211 did not convert to an agonist in the presence of protein kinase A (PKA) activators and showed high antiprogestagenic activity on both PR isoforms PR-A and PR-B. This high antiprogestagenic activity could also be demonstrated in several in vivo models. Furthermore, this compound displayed only marginal antiglucocorticoid effects. In tumor models ZK 230211 exhibited strong antiproliferative action. The pharmacological properties of ZK 230211 may prove useful in the treatment of endometriosis, leiomyomas, breast cancer, and in hormone replacement therapy.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mifepristone	Progesterone receptor	IC 50 (nM)	0.028	N/A	N/A	Details
Mifepristone	Progesterone receptor	IC 50 (nM)	0.025	N/A	N/A	Details