17beta-Arylsulfonamides of 17beta-aminoestra-1,3,5(10)-trien-3-ol as highly potent inhibitors of steroid sulfatase.

Article Details

Citation

Copy to clipboard

Mostafa YA, Taylor SD

17beta-Arylsulfonamides of 17beta-aminoestra-1,3,5(10)-trien-3-ol as highly potent inhibitors of steroid sulfatase.

Bioorg Med Chem. 2012 Feb 15;20(4):1535-44. doi: 10.1016/j.bmc.2011.12.036. Epub 2012 Jan 5.

PubMed ID

22264754 [ View in PubMed

]

Abstract

Steroid sulfatase (STS) catalyzes the desulfation of biologically inactive sulfated steroids to yield biologically active desulfated steroids and is currently being examined as a target for therapeutic intervention for the treatment of breast and other steroid-dependent cancers. Here we report the synthesis of a series of 17beta-arylsulfonamides of 17beta-aminoestra-1,3,5(10)-trien-3-ol and their evaluation as inhibitors of STS. Some of these compounds are among the most potent reversible STS inhibitors reported to date. Introducing n-alkyl groups into the 4'-position of the 17beta-benzenesulfonamide derivative resulted in an increase in potency with the n-butyl derivative exhibiting the best potency with an IC(50) of 26 nM. A further increase in carbon units (to n-pentyl) resulted in a decrease in potency. Branching of the 4'-n-propyl group resulted in a decrease in potency while branching of the 4'-n-butyl group (to a tert-butyl group) resulted in a slight increase in potency (IC(50)=18 nM). Studies with 3'- and 4'-substituted substituted 17beta-benzenesulfonamides with small electron donating and electron withdrawing groups revealed the 3'-bromo and 3'-trifluoromethyl derivatives to be excellent inhibitors with IC(50)'s of 30 and 23 nM, respectively. The 17beta-2'-naphthalenesulfonamide was also an excellent inhibitor (IC(50)=20 nM) while the 17beta-4'-phenylbenzenesulfonamide derivative was the most potent inhibitor of all the compounds studied with an IC(50) of 9 nM.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Irosustat	Steryl-sulfatase	IC 50 (nM)	350	N/A	N/A	Details