1035353-90-2Relevant academic research and scientific papers
Synthesis and biological evaluation of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors based on a thieno[2,3-d] pyrimidin-4(3H)-one core
Lilienkampf, Annamaria,Karkola, Sampo,Alho-Richmond, Sari,Koskimies, Pasi,Johansson, Nina,Huhtinen, Kaisa,Vihko, Kimmo,W?h?l?, Kristiina
experimental part, p. 6660 - 6671 (2010/04/28)
Many breast tumors are hormone-dependent, and estrogens, especially estradiol (E2), have a pivotal role in their growth and development. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a key enzyme in the biosynthesis of female sex steroids, catalyzing the NADPH-dependent reduction of estrone into biologically active estradiol. In this study, a library of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-one based compounds was synthesized, and the biological activities against 17β-HSD1 in a cell-free and in a cell-based assay were evaluated. Several thieno[2,3-d]pyrimidin-4(3H)-one based compounds, at 0.1 and 1 μM test concentrations, were found to be potent 17β-HSD1 inhibitors. For example, 4-(3-hydroxyphenylthio)-1,2,7,8,9,10,11,13-octahydro-13-oxo-[1] benzothieno[2′,3′:4,5]-pyrimido[1,2-a]azepine-3-carboxaldehyde (7f) is one of the most potent nonsteroidal 17β-HSD1 inhibitors reported to date with 94% inhibition of the recombinant enzyme at 0.1 μM test concentration. Importantly, the majority of these compounds exhibited excellent selectivity over the oxidative isoform 17β-HSD2 and lacked estrogenic effects in an estrogen receptor (ER) binding assay.
