TY  - JOUR
AU  - Jójárt, Rebeka
AU  - Pécsy, S.
AU  - Keglevich, György
AU  - Szécsi, Mihály
AU  - Laczkó-Rigó, Réka
AU  - Laczka, Csilla
AU  - Kecskeméti, Gábor
AU  - Mernyák, Erzsébet
TI  - Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors
JF  - BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
J2  - BEILSTEIN J ORG CHEM
VL  - 14
ET  - 0
PY  - 2018
SP  - 2838
EP  - 2845
PG  - 8
SN  - 1860-5397
DO  - 10.3762/bjoc.14.262
UR  - https://m2.mtmt.hu/api/publication/30331520
ID  - 30331520
N1  - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary            
            Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, H-1521, Hungary            
            1st Department of Medicine, University of Szeged, Korányi fasor 8-10, Szeged, H-6720, Hungary            
            Membrane protein research group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary            
            Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary            
            Cited By :9            
            Export Date: 26 August 2021            
            CODEN: BJOCB            
            Correspondence Address: Mernyák, E.; Department of Organic Chemistry, Dóm tér 8, Hungary; email: bobe@chem.u-szeged.hu
AB  - 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.
LA  - English
DB  - MTMT
ER  -