Synthesis and SAR study of novel pseudo-steroids as potent and selective progesterone receptor antagonists.

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Jain N, Allan G, Linton O, Tannenbaum P, Chen X, Xu J, Zhu P, Gunnet J, Demarest K, Lundeen S, Murray W, Sui Z

Synthesis and SAR study of novel pseudo-steroids as potent and selective progesterone receptor antagonists.

Bioorg Med Chem Lett. 2009 Jul 15;19(14):3977-80. doi: 10.1016/j.bmcl.2009.01.095. Epub 2009 Jan 31.

PubMed ID
19217285 [ View in PubMed
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Abstract

Synthesis of novel 7-pseudo-steroids 1c has been achieved from trenbolone 3 via an efficient 14 step sequence with overall yields of 10-15%. Various substitutions were incorporated at both the aromatic side chain as well as the D ring. The orientation of aromatic side chain at C10 plays a crucial role for progesterone receptor (PR) activity. Compound 2a (T47D=1nM) with -NMe(2) para to the aromatic group along with spirofurane groups in the D ring was the optimal substitution. All compounds were also evaluated for glucocorticoid receptor (GR) antagonist activities in vivo in a rat and found efficacious in uterine complement C3 assay via the oral route of administrations.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MifepristoneGlucocorticoid receptorIC 50 (nM)1.6N/AN/ADetails
MifepristoneProgesterone receptorIC 50 (nM)1.4N/AN/ADetails