1630-82-6Relevant articles and documents
Synthesis and structure–activity relationships of 2- and/or 4-halogenated 13β- and 13α-estrone derivatives as enzyme inhibitors of estrogen biosynthesis
Bacsa, Ildikó,Herman, Bianka Edina,Jójárt, Rebeka,Herman, Kevin Stefán,W?lfling, János,Schneider, Gyula,Varga, Mónika,T?mb?ly, Csaba,Ri?ner, Tea Lani?nik,Szécsi, Mihály,Mernyák, Erzsébet
, p. 1271 - 1282 (2018)
Ring A halogenated 13α-, 13β-, and 17-deoxy-13α-estrone derivatives were synthesised with N-halosuccinimides as electrophile triggers. Substitutions occurred at positions C-2 and/or C-4. The potential inhibitory action of the halogenated estrones on human aromatase, steroid sulfatase, or 17β-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Potent submicromolar or low micromolar inhibitors were identified with occasional dual or multiple inhibitory properties. Valuable structure–activity relationships were established from the comparison of the inhibitory data obtained. Kinetic experiments performed with selected compounds revealed competitive reversible inhibition mechanisms against 17β-hydroxysteroid dehydrogenase 1 and competitive irreversible manner in the inhibition of the steroid sulfatase enzyme.
A-ring substituted 17β-arylsulfonamides of 17β-aminoestra-1,3,5(10)-trien-3-ol as highly potent reversible inhibitors of steroid sulfatase
Mostafa, Yaser A.,Kralt, Braden,Rao, Praveen P.N.,Taylor, Scott D.
, p. 5681 - 5692 (2015)
Steroid sulfatase (STS) catalyzes the hydrolysis of the sulfate ester group in biologically inactive sulfated steroids to give biologically active steroids. Inhibitors of STS are considered to be potential therapeutics for treating hormone-dependent cancers such as ER+ breast cancer. A series of 4-substituted 17β-arylsulfonamides of 17β-aminoestra-1,3,5(10)-trien-3-ol were prepared and examined as STS inhibitors. The presence of a NO2 or Br at the 2-position of the A-ring resulted in a decrease in potency compared to their A-ring-unsubstituted counterparts. However the presence of a nitro group or fluorine atom at the 4-position of the A-ring resulted in an increase in potency and one of these compounds exhibited a Kiapp value of 1 nM. Modeling studies provided insight into how these compounds interact with active site residues. The anti-proliferative activity of the 3′-Br, 3′-CF3, 4-NO2-3′-Br and 4-NO2-3′-CF3 derivatives were examined using the NCI 60-cell-line panel and found to have mean graph midpoint values of 1.9-3.4 μM.
Chemoselective Suzuki-Miyaura reactions of 4-bromo-3-O-triflyl-estrone. Synthesis and atropisomerism of arylated estrones
Jopp, Stefan,Wallaschkowski, Tina,Ehlers, Peter,Frank, Eva,Schneider, Gyula,W?lfling, János,Mernyák, Erzsébet,Villinger, Alexander,Langer, Peter
, p. 2825 - 2836 (2018)
4-Bromo-3-O-triflyl-estrone has been synthesized in 2 steps from estrone and was successfully employed in chemoselective palladium catalysed Suzuki-Miyaura reactions. Mono- and bis-arylations were carried out selectively by variation of ligands and solven
Structure-Based Design and Synthesis of New Estrane-Pyridine Derivatives as Cytochrome P450 (CYP) 1B1 Inhibitors
Dutour, Rapha?l,Cortés-Benítez, Francisco,Roy, Jenny,Poirier, Donald
, p. 1159 - 1164 (2017)
Inhibition of cytochrome P450 (CYP) 1B1 is a promising therapeutic strategy, as such an inhibitor could modulate the bioactivation of procarcinogens while reducing drug resistance. Based on docking studies, the synthesis of 12 estra-1,3,5(10)-triene derivatives containing a pyridin-3-/4-yl moiety at position C2, C3, or C4 was performed, and we measured their inhibitory activity on CYP1B1 using the ethoxyresorufin-O-deethylase (EROD) assay. The position of the nitrogen atom in the aromatic ring has little influence on their inhibition potency, but compounds with a pyridinyl at C2 of the steroid nucleus are more potent CYP1B1 inhibitors than those with a pyridinyl at C3 or C4. Estradiol derivatives (OH at C17β) are also 10-fold more potent inhibitors than estrone derivatives (carbonyl at C17). Thus, 2-(pyridin-3-yl)-estradiol (4a) is the best CYP1B1 inhibitor (IC50 = 0.011 μM) from this series of compounds, and the best steroid inhibitor reported until now. It is also 7.5-fold more potent than the well-known nonsteroidal CYP1B1 inhibitor α-naphthoflavone (IC50 = 0.083 μM).
Synthesis, functionalization and biological activity of arylated derivatives of (+)-estrone
Ivanov, Anton,Ejaz, Syeda Abida,Shah, Syed Jawad Ali,Ehlers, Peter,Villinger, Alexander,Frank, Eva,Schneider, Gyula,W?lfling, János,Rahman, Qamar,Iqbal, Jamshed,Langer, Peter
, p. 949 - 962 (2017/02/05)
Various novel arylated estrone derivatives, such as 2-aryl-, 4-aryl- and 2,4-diaryl-estrones, by Suzuki-Miyaura reactions. While the synthesis of 4-arylestrones could be carried out under standard conditions, the synthesis of 2-arylestrones and 2,4-diarylestrones required a thorough optimization of the conditions and it proved to be important to use sterically encumbered biaryl ligands. The best results were obtained by the use of RuPhos. Combination of developed Suzuki coupling reactions with subsequent cyclization reactions afforded more complex hybrid structures, containing dibenzofuran, benzocoumarin and steroid moieties. These derivatives were tested as pancreatic lipase inhibitors and it was found that most of the compounds exhibited inhibition of pancreatic lipase but the maximum inhibitory potential was shown by 4-arylestrones. All of the synthesized derivatives showed inhibitory values in the range of 0.82 ± 0.01–59.7 ± 3.12 μM. The biological activity was also rationalized on the bases of docking studies.
