Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

Jójárt, R. [Jójárt, Rebeka (Szerves kémia), author] Department of Organic Chemistry (USZ / TTIK / KI); Pécsy, S.; Keglevich, G. [Keglevich, György (Szerves kémia, fo...), author] Department of Organic Chemistry and Technology (BUTE / FCTB); Szécsi, M. [Szécsi, Mihály (Szteroidok analit...), author] First Department of Internal Medicine (USZ / ÁOK); Rigó, R. [Laczkó-Rigó, Réka, author]; Ozvegy-Laczka, C. [Laczka, Csilla (Biokémia, molekul...), author] Enzim_405 (RCNS / EI); Kecskeméti, G. [Kecskeméti, Gábor (Analitika), author] Department of Medical Chemistry (USZ / ÁOK); Mernyák, E. ✉ [Mernyák, Erzsébet (Szerves kémia), author] Department of Organic Chemistry (USZ / TTIK / KI)

English Scientific Article (Journal Article)
Published: BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY 1860-5397 14 pp. 2838-2845 2018
  • SJR Scopus - Organic Chemistry: Q2
    Novel 2- or 4-phosphonated 13 alpha-estrone derivatives were synthesized via the Hirao reaction. Bromo regioisomers (2- or 4-) of 13 alpha-estrone and its 3-benzyl or 3-methyl ether were reacted with diethyl phosphite or diphenylphosphine oxide using Pd(PPh3)(4) as catalyst under microwave irradiation. The influence of the new compounds on the transport function of the organic anion transporting polypeptide OATP2B1 was investigated by measuring Cascade Blue uptake. Derivatives bearing a 3-benzyl ether function displayed substantial submicromolar OATP2B1 inhibitory activity. The inhibitory effects of the compounds on human placental steroid sulfatase (STS) and 17 beta-hydroxysteroid dehydrogenase type 1 isozyme (17 beta-HSD1) were investigated by in vitro radiosub-strate incubation methods. None of the test compounds inhibited the STS markedly. The structure-activity relationship evaluation revealed that 2-substituted 3-hydroxy derivatives are able to inhibit the 17 beta-HSD1 enzyme with submicromolar IC50 values. Dual OATP2B1 and 17 beta-HSD1 inhibitors have been identified.
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    2021-06-17 03:22