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Issue 18, 2005
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Synthesis of a non-hydrolyzable estrone sulfate analogue bearing the difluoromethanesulfonamide group and its evaluation as a steroid sulfatase inhibitor

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Abstract

Steroid sulfatase (STS) catalyzes the hydrolyis of steroidal sulfates such as estrone sulfate (ES1) and is considered to be an attractive target in the treatment of steroid dependent cancers. A non-hydrolyzable estrone sulfate (ES1) analogue bearing an α,α-difluorosulfonamide moiety at the 3-position on the A-ring, compound 7, was synthesized. Key to the success of this synthesis was the first use of the allyl group as a sulfonamide protecting group. The pKa of this ES1 mimic in 0.1 M bis-tris propane, 10% DMSO was determined to be 8.05 using 19F NMR. Compound 7 is a reversible inhibitor with a Ki similar to that of its sulfonate analogue at pH 7.0. It is more potent than its nonfluorinated sulfonamide analogue and, its inhibitory potency increases with increasing pH, a trend opposite to that of other STS inhibitors. Possible reasons for this are presented.

Graphical abstract: Synthesis of a non-hydrolyzable estrone sulfate analogue bearing the difluoromethanesulfonamide group and its evaluation as a steroid sulfatase inhibitor

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Publication details

The article was received on 22 Jun 2005, accepted on 20 Jul 2005 and first published on 04 Aug 2005


Article type: Paper
DOI: 10.1039/B508852F
Org. Biomol. Chem., 2005,3, 3329-3335

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    Synthesis of a non-hydrolyzable estrone sulfate analogue bearing the difluoromethanesulfonamide group and its evaluation as a steroid sulfatase inhibitor

    Y. Liu, V. Ahmed, B. Hill and S. D. Taylor, Org. Biomol. Chem., 2005, 3, 3329
    DOI: 10.1039/B508852F

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