Synthesis of simplified hybrid inhibitors of type 1 17beta-hydroxysteroid dehydrogenase via cross-metathesis and sonogashira coupling Reactions

Organic Letters
Marie Bérubé, Donald Poirier

Abstract

[structure: see text] The inhibitor of type 1 17beta-hydroxysteroid dehydrogenase EM-1745 (1) exhibits affinity for both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding domains. However, to increase its bioavailability, this compound needs to be simplified. The efficient and convergent synthesis of simplified substrate/cofactor hybrid inhibitors (compounds 2) involving a cross-metathesis and a Sonogashira coupling reaction as key steps is described. Compounds 2a-c were also tested as enzyme inhibitors and compared to EM-1745.

References

Dec 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·V Luu-TheF Labrie
May 29, 2000·Chemistry : a European Journal·M RottlanderP Knochel
Jun 1, 2001·The Journal of Steroid Biochemistry and Molecular Biology·V Luu-The
Mar 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·D S TarbellB M Pope

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Citations

Dec 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teresa KasererDaniela Schuster
Jul 28, 2009·The Journal of Steroid Biochemistry and Molecular Biology·Paul J A MichielsUlrich L Günther
Sep 1, 2014·Steroids·Dorota Czajkowska-SzczykowskaAgnieszka Wojtkielewicz
Jun 4, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Atul GuptaArvind S Negi
Feb 3, 2006·Natural Product Reports·James R Hanson
Jan 27, 2017·Chemical Communications : Chem Comm·Jordan AtchisonJohn F Callan
Mar 26, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marie BérubéDonald Poirier
Mar 3, 2009·Annals of the New York Academy of Sciences·Marc MeierJerzy Adamski
Mar 14, 2017·The Journal of Steroid Biochemistry and Molecular Biology·Katharina R BeckAlex Odermatt
Feb 20, 2007·Chemical Reviews·Rafael Chinchilla, Carmen Najera
Dec 15, 2017·The Journal of Organic Chemistry·Peihong XiaoZhenlei Song

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