Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

Ildikó Bacsa, Rebeka Jójárt, J. Wölfling, G. Schneider, Bianka Edina Herman, Mihály Szécsi, E. Mernyák

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4 Citations (Scopus)

Abstract

Novel 13α-estrone derivatives were synthesized by Sonogashira coupling. Transformations of 2- or 4-iodo regioisomers of 13α-estrone and its 3-methyl ether were carried out under different conditions in a microwave reactor. The 2-iodo isomers were reacted with para-substituted phenylacetylenes using Pd(PPh3)4 as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives could be achieved by changing the catalyst to Pd(PPh3)2Cl2. The product phenethynyl derivatives were partially or fully saturated. Compounds bearing a phenolic OH group furnished benzofurans under the conditions used for the partial saturation. The inhibitory effects of the compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by an in vitro radiosubstrate incubation method. Certain 3-hydroxy-2-phenethynyl or -phenethyl derivatives proved to be potent 17β-HSD1 inhibitors, displaying submicromolar IC50 values.

Original languageEnglish
Pages (from-to)1303-1309
Number of pages7
JournalBeilstein Journal of Organic Chemistry
Volume13
DOIs
Publication statusPublished - Jun 30 2017

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Keywords

  • 13α-estrone
  • 17β-HSD1 inhibition
  • Benzofuran
  • Partial saturation
  • Sonogashira coupling

ASJC Scopus subject areas

  • Organic Chemistry

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