90857-55-9Relevant academic research and scientific papers
Synthesis, Receptor Binding, and Tissue Distribution of 7α- and 11β-Substituted (17α,20E)- and (17α,20Z)-21-125I>odo-19-norpregna-1,3,5(10),20- tetraene-3,17-diols
Ali, H.,Rousseau, J.,Ghaffari, M. A.,Lier, J. E. van
, p. 854 - 860 (1991)
The 11β-methoxy, 11β-ethoxy, and 7α-methyl derivatives of the isomeric (17α,20E)- and (17α,20Z)-(iodovinyl)estradiols 3 and 6, and their no-carrier-added iodovinyl analogues, were evaluated for their relative target-tissue retension and binding affinity for the estrogen receptor.The isomeric iodovinyl and iodovinyl derivatives were prepared via destannylation of the corresponding tributylstannyl precursors in the presence of H2O2 or chloroamine-T, with retension of configuration.The 20Z isomers 6 exhibited slightly higher receptor binding affinities than the 20E isomers 3, with all eight isomeric products giving relative binding affinity values in the 20-50 range.The 11β- and 7α-substituted (iodovinyl)estradiols gave substantially higher estrogen receptor-mediated uterus uptake as compared to the nonsubstituted parent molecule.Synergism between the effect of 11β- or 7α-substituents and the configuration of the iodovinyl group was evident from the in vivo distribution pattern of -3 and -6.The best uterus uptake was observed, at 2 h postinjection, with the 20E isomer of 11β-methoxy derivative 3b.However, at 5 h postinjection the 20Z isomer 6b reached higher uterus concentrations than the 20E isomer 3b, and furthermore, these values are now comparable to those observed with the 20Z isomer of the 11β-ethoxy derivative 6c.In the case of the 7α-methyl derivatives the differences in in vivo stability between the 20E and 20Z isomers was less pronounced, whereas the 20Z isomer 6d reached somewhat higher uterus to blood as well as nontarget ratios.
Synthesis and evaluation of (17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 -diol and (17 alpha,20E)-21-[125I]iodo-11 beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (17 alpha-(iodovinyl)estradiol derivatives) as high specific activity potential radiopharmaceuticals.
Nakatsuka, Iwao,Ferreira, Nelson L.,Eckelman, W. C.,Francis, B. E.,Rzeszotarski, W. J.,et al.
, p. 1287 - 1291 (2007/10/02)
Two 17 alpha-[125I]iodovinyl estradiol derivatives 4b,d possessing high specific activity have been prepared and tested as potential radiopharmaceuticals. The use of the 3-acetyl derivatives 2c,e and the replacement of iodine monochloride with sodium iodide and Chloramine-T in THF/phosphate buffer (pH 7.0) permitted us to synthesize no-carrier-added (17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-d iol (4b) and (17 alpha,20E)-21-[125I]iodo-11 beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (4d) with 50% radiochemical yield and high purity. Although the specific activity represents only half of the theoretical value in some cases, this modified approach is a substantial improvement over the previously published method. Our preliminary distribution studies indicate that although both 4b and 4d localize in the tissues known to have a large concentration of estrogen receptors, 4d accumulates in higher amounts in target tissues and provides a high target to nontarget ratio.
