123715-80-0Relevant academic research and scientific papers
Synthesis of 2-[11C]methoxy-3,17β-O,O-bis(sulfamoyl) estradiol as a new potential PET agent for imaging of steroid sulfatase (STS) in cancers
Wang, Min,Xu, Lu,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang
, p. 864 - 870 (2012/07/14)
Steroid sulfatase (STS) catalyzes the hydrolysis of steroid sulfates to estrones, the main source of estrogens in tumors. Carbonic anhydrase II (CAII) is highly expressed in red blood cells through a coordination of the monoanionic form of the sulfamate moiety to the zinc atom in the enzyme active site, and CAII is highly expressed in several tumors. 2-Methoxy-3,17β-O,O- bis(sulfamoyl)estradiol (5) is a dual-function STS-CAII inhibitor inhibited STS with 39 nM IC50 value selectively over CAII with 379 nM IC 50 value. This compound exhibited potent antiproferative activity with mean graph midpoint value of 87 nM in the NCI 60-cell-line panel, and antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model as well. The compound has been recently developed as a multitargeted anticancer agent. Both STS and CAII are over-expressed in cancers and have become attractive targets for cancer treatment and molecular imaging of cancer. Here we report the first design and synthesis of 2-[11C]methoxy-3,17β- O,O-bis(sulfamoyl)estradiol ([11C]5) as a new potential imaging agent for biomedical imaging technique positron emission tomography (PET) to image STS in cancers. The authentic standard 5 was synthesized from 17β-estradiol by published procedures in 5 steps with 40% overall chemical yield. The precursor 2-hydroxy-3,17β-O,O-bis(sulfamoyl)estradiol (14a) for radiolabeling was synthesized from 17β-estradiol in 10 steps with 5% overall chemical yield. The target tracer [11C]5 was prepared from the precursor 14a with [11C]CH3OTf through O-[ 11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) purification in 40-50% radiochemical yields based on [ 11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.
Ortho-Formylation of estrogens. Synthesis of the anti-cancer agent 2-methoxyestradiol
Akselsen, ?yvind W.,Hansen, Trond Vidar
scheme or table, p. 7738 - 7742 (2011/10/13)
Several estrogens were mono-formylated using a mixture of paraformaldehyde, MgCl2, and Et3N in refluxing THF. In all cases, the 2-isomer was formed as the major product with high regioselectivity compared to the 4-isomer. Excellent to high yields were obtained in all examples except one. The method was applied for an efficient synthesis of the anti-cancer agent 2-methoxyestradiol.
Effects of altering the electronics of 2-methoxyestradiol on cell proliferation, on cytotoxicity in human cancer cell cultures, and on tubulin polymerization
Edsall, Allison B.,Mohanakrishnan, Arasambattu K.,Yang, Donglai,Fanwick, Philip E.,Hamel, Ernest,Hanson, Arthur D.,Agoston, Gregory E.,Cushman, Mark
, p. 5126 - 5139 (2007/10/03)
A series of new analogues of 2-methoxyestradiol (1) were synthesized to further elucidate the relationships between structure and activity. The compounds were designed to diminish the potential for metabolic deactivation at positions 2 and 17 and were analyzed as inhibitors of tubulin polymerization and for cytotoxicity. 17α-Methyl-β-estradiol (30), 2-propynyl-17α- methylestradiol (39), 2-ethoxy-17-(1′-methylene)estra-1,3,5(10)-triene-3- ol (50) and 2-ethoxy-17α-methylestradiol (51) showed similar or greater tubulin polymerization inhibition than 2-methoxyestradiol (1) and contained moieties that are expected to inhibit deactivating metabolic processes. All of the compounds tested were cytotoxic in the panel of 55 human cancer cell cultures, and generally, the derivatives that displayed the most activity against tubulin were also the most cytotoxic.
2-Methoxyestradiol and analogs as novel antiproliferative agents: Analysis of three-dimensional quantitative structure-activity relationships for DNA synthesis inhibition and estrogen receptor binding
Hughes, Richard A.,Harris, Trudi,Altmann, Emile,McAllister, David,Vlahos, Ross,Robertson, Alan,Cushman, Mark,Wang, Zhiqiang,Stewart, Alastair G.
, p. 1053 - 1069 (2007/10/03)
2-Methoxyestradiol (2-MEO), a metabolite of estrogen, is an attractive lead compound for the development of novel antitumor and anti-inflammatory agents, because it embodies antiproliferative and antiangiogenic activities in one molecule. However, the aff
2-(hydroxyalkyl)estradiols: Synthesis and biological evaluation
Lovely, Carl J.,Gilbert, Nancy E.,Liberto, Muriel M.,Sharp, Damon W.,Lin, Young C.,Brueggemeier, Robert W.
, p. 1917 - 1923 (2007/10/03)
Synthetic estrogens possessing hydroxyalkyl side chains at the C-2 position of the A-ring were designed in order to further elucidate the structural and electronic requirements of the estrogen receptor to A-ring modifications. Furthermore, these compounds were envisaged as being stable analogs of the estradiol metabolite 2-hydroxyestradiol. The homologous series of 2-(hydroxy-alkyl)estradiols 1-3 has been prepared by chain extension of 2- formylestradiol 6, which, in turn, was prepared via ortholithiation of estradiol. The substituted estradiols 1-3 were assayed for their abilities to bind to the estrogen receptor in MCF-7 cells and induce estrogen-responsive gene expression. The estradiol homologs exhibited significantly weaker affinity than estradiol for the MCF-7 cell estrogen receptor, with relative binding affinities (estradiol = 100) ranging from 1.11 for 2- (hydroxymethyl)estradiol (1) to 0.073 for 2-(hydroxypropyl)estradiol (3). The relative activities for mRNA induction of the pS2 gene by the estradiol homologs closely parallel the relative binding affinities for the estrogen receptor in MCF-7 cells. 2-(Hydroxymethyl)estradiol (1) exhibited similar estrogen receptor affinity and pS2 gene induction to the catechol estrogen 2- hydroxyestradiol and may prove useful in examination of the further biological effects of 2-hydroxyestrogen homologs.
Synthesis of '3+1' mixed-ligand oxorhenium(V)complexes containing modified 3,17β-estradiol
Wuest, Frank,Spies, Hartmut,Johannsen, Bernd
, p. 2729 - 2734 (2007/10/03)
Two rhenium '3+1' mixed-ligand complexes bearing an estradiol moiety were prepared. The small-sized rhenium chelate units were introduced by two different rhenium precursors to give stable complexes in satisfactory yields.
Synthesis of 2-substituted hydroxyalkyl and aminoalkyl estradiols
Lovely, Carl J.,Brueggemeier, Robert W.
, p. 8735 - 8738 (2007/10/02)
An homologous series of 2-substituted hydroxyalkyl and aminoalkyl estradiols have been prepared by elaboration of the formylated estradiol derivative 10.
Formylation of Oestrogens
Pert, Derek J.,Ridley, Damon D.
, p. 405 - 419 (2007/10/02)
Reimer-Tiemann formylations of oestradiol and oestrone were investigated and, whilst substitution was effected under certain conditions to give mixtures of 2-and 4-formyloestrogens, yields were very low and the method was unsuitable for preparative purposes.Regioselective methods were developed and 2-formyloestradiol was conveniently prepared from oestradiol by formylation of the lithio derivative of the bis(methoxymethyl) ether and removal of the protecting groups with the hydrochloric acid. 4-Formyloestradiol was prepared by a sequence of reactions starting with the methoxyethyl ether of 4-bromooestradiol, then metal-halogen interconversion, formylation with N-methylformanilide, and removal of the protecting group.A number of related derivatives, including 2-formyloestriol, were prepared.
