Configuration of Dienestrol

Doyle, Thomas D.; Stewart, J.M.; Filipescu, Nicolae; Benson, Walter R.

doi:10.1002/jps.2600640922

Cited by 8 publications

(1 citation statement)

References 6 publications

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“…Compounds in the set were generated from the X-ray crystal structures or by modification of the crystal structure of a similar compound using the SYBYL BUILD option. X-ray crystal data were available for compounds 1 , 2 , 8 , and 9 , 11 , and 17 . Compounds 4 − 6 , 29 , and 30 were generated from the crystal structure of compound 2 .…”

Section: Computational Detailsmentioning

confidence: 99%

Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r²-Guided Region Selection Approach

et al. 1998

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A newly developed comparative molecular field analysis (CoMFA) technique, the cross-validated r2-guided region selection (CoMFA/q2-GRS) method, has been used to build a quantitative structure-activity relationship (3D-QSAR) for nonsteroidal estrogen receptor (ER) ligands. Ligands included in this study belong to a series of diethylstilbestrol (DES) and indenestrol analogues whose affinities for the mouse ER (mER) have been determined in our laboratory. The final model utilized 30 compounds and yielded a q2GRS (cross-validated r2, guided region selection) of 0.796, as compared to a q2 of 0.720 for conventional CoMFA, with a standard error of prediction of 0.594 at 3 principal components. This model was used to visualize steric and electrostatic features of the ligands that correspond with ER binding affinity. Results obtained from the CoMFA steric and electrostatic plots of this model have also been compared to information from the ER binding affinities of substituted estradiol analogues. This is in an effort to determine structural features of compounds in the CoMFA analysis that may correspond to those of the estradiol analogues and to further clarify the mode of binding of nonsteroidal ER ligands.

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Section: Computational Detailsmentioning

confidence: 99%

Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r²-Guided Region Selection Approach

et al. 1998

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Synthese und Testung der potentiellen östrophilen Cytostatica 2,3‐Epoxy‐3,4‐bis(4′‐acetoxyphenyl)hexen‐4 und 2,3,4,5‐Bis‐epoxy‐3,4‐bis(4′‐acetoxyphenyl)hexan

Schneider

Schönenberger

Michel

et al. 1982

Archiv der Pharmazie

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Durch Epoxidierung von 3,4-Bis(4'-acetoxyphenyl)-E,E-hexadien-2,4(3a) werden 2,3-Epoxy-3,4-bis(4'-acetoxyphenyl)hexen-4 (4a) und 2,3,4,5-Bis-epoxy-3,4-bis(4'-acetoxyphenyl)hexan (5a) erhalten. 3a, 4a und Sa hemmen die 3H-Ostradiol-Rezeptor-Wechselbeziehung kompetitiv (3a>4a>5a) und das Wachstum eines auf thymusaplastische Mause transplantierten menschlichen Mammacarcinoms (3a,4aXa). Die Feststellung, da13 die Uberfiihrung von Diethylstilbostrol (DES (1) relative Bindungsaffinitat (RBA) = 41,0, Ostradiol, RBA = 100) in 3,4-Bis(4'-hydroxyphenyl)3,4-epoxy-hexan (2, RBA = 38.0) zu keiner nennenswerten Veranderung der Ostradiolrezeptor-Affinitat fiihrt'), und die starke Wirkung von 2 an verschiedenen hormonabhangigen Mammatumormodellen') veranlaI3ten uns zur Synthese und pharmakologischen Priifung des Mono-und Bisepoxids von Dienostrol (3), 2,3-Epoxy-3,4-bis(4'-acetoxyphenyl)hexen-4 (4a) und 2,3, 4,5-Bis-epoxy-3,4-bis(4'-acetoxypheny1)hexan (5a). Wir diskutieren die Bildung der potentiell cytotoxischen Metabolite 2, 4 und 5 (s. Formelschema) als eine mogliche Ursache der mammatumorhemmenden Eigenschaften von DES (1) und Dienostrol (DIES, 3). Einen Hinweis fur diese Theorie liefert der Nachweis genotoxischer Eigenschaften fur 1 und 3 im ,,sister chromatid exchange experiment" (SCE-Test) nach metabolischer Aktivierung'). Syntheses and Evaluation of the Potentially Oestrophilic

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Metabolism of diethylstilbestrol in the C3H mouse: Chromatographic systems for the quantitative analysis of DES metabolic products

et al. 1978

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Configuration of Dienestrol

Cited by 8 publications

References 6 publications

Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r²-Guided Region Selection Approach

Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r²-Guided Region Selection Approach

Synthese und Testung der potentiellen östrophilen Cytostatica 2,3‐Epoxy‐3,4‐bis(4′‐acetoxyphenyl)hexen‐4 und 2,3,4,5‐Bis‐epoxy‐3,4‐bis(4′‐acetoxyphenyl)hexan

Metabolism of diethylstilbestrol in the C3H mouse: Chromatographic systems for the quantitative analysis of DES metabolic products

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Configuration of Dienestrol

Cited by 8 publications

References 6 publications

Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r2-Guided Region Selection Approach

Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r2-Guided Region Selection Approach

Synthese und Testung der potentiellen östrophilen Cytostatica 2,3‐Epoxy‐3,4‐bis(4′‐acetoxyphenyl)hexen‐4 und 2,3,4,5‐Bis‐epoxy‐3,4‐bis(4′‐acetoxyphenyl)hexan

Metabolism of diethylstilbestrol in the C3H mouse: Chromatographic systems for the quantitative analysis of DES metabolic products

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Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r²-Guided Region Selection Approach

Three-Dimensional Quantitative Structure−Activity Relationship Study of Nonsteroidal Estrogen Receptor Ligands Using the Comparative Molecular Field Analysis/Cross-Validated r²-Guided Region Selection Approach