D-ring modified estrone derivatives as novel potent inhibitors of steroid sulfatase

Delpnine S. Fischer, L. W. Lawrence Woo, Mary F. Mahon, Atul Purohit, Michael J. Reed, Barry V. L. Potter

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62 Citations (SciVal)


A series of novel D-ring modified derivatives of estrone was synthesized and tested as inhibitors of steroid sulfatase (STS). The steroidal D-ring was cleaved via an iodoform reaction and thermal condensation of the resulting marrianolic acid derivative gave 16,17-seco-estra-1,3,5(10)-triene-16,17-imide derivatives, where a piperidinedione moiety is in place of the D-ring. This synthetic approach was found to give a higher overall yield than the literature method of Beckmann rearrangement. A range of alkyl side chains have been introduced on the nitrogen atom of the imido-ring and the corresponding 3-O-sulfamates synthesized. The new D-ring modified estrone derivatives bearing a propyl (39) and a 1-pyridin-3-ylmethyl (46) moiety had IC50 values of 1 nM when tested in placental microsomes for the inhibition of STS. These compounds are therefore up to 18-fold more potent than EMATE, the very first highly potent irreversible steroidal STS inhibitor.
Original languageEnglish
Pages (from-to)1685-1700
JournalBioorganic and Medicinal Chemistry
Issue number8
Publication statusPublished - 2003


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