Synthesis, characterization and biological evaluation of some novel 17-isoxazoles in the estrone series

Dóra Kovács, Zalán Kádár, Gerg Mótyán, G. Schneider, J. Wölfling, I. Zupkó, E. Frank

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Regioselective 1,3-dipolar cycloadditions of different aryl nitrile oxides to mestranol were carried out to furnish novel steroidal 17α-isoxazoles in good to excellent yields. Copper(I) was found to be an efficient catalyst, accelerating the intermolecular ring-closures and leading exclusively to 3,5-disubstituted isoxazoles. The yields of the cycloadducts, however, were influenced by the substituents on the aromatic moiety of the 1,3-dipoles. Moreover, dehydration of the primary products resulted in the corresponding Δ16,17 exo-heterocyclic derivatives. All the synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative effects relative to three human malignant cell lines (HeLa, MCF7 and A2780).

Original languageEnglish
Pages (from-to)1075-1085
Number of pages11
JournalSteroids
Volume77
Issue number11
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Isoxazoles
Estrone
Mestranol
Nitriles
Cycloaddition
Cycloaddition Reaction
Dehydration
Oxides
Copper
Cells
Pharmacology
Derivatives
Cell Line
Catalysts
In Vitro Techniques

Keywords

  • Cycloaddition
  • Cytotoxic activity
  • Isoxazoles
  • Nitrile oxides

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis, characterization and biological evaluation of some novel 17-isoxazoles in the estrone series. / Kovács, Dóra; Kádár, Zalán; Mótyán, Gerg; Schneider, G.; Wölfling, J.; Zupkó, I.; Frank, E.

In: Steroids, Vol. 77, No. 11, 09.2012, p. 1075-1085.

Research output: Contribution to journalArticle

@article{09663d91e0cd4361b3832a8a81628f70,
title = "Synthesis, characterization and biological evaluation of some novel 17-isoxazoles in the estrone series",
abstract = "Regioselective 1,3-dipolar cycloadditions of different aryl nitrile oxides to mestranol were carried out to furnish novel steroidal 17α-isoxazoles in good to excellent yields. Copper(I) was found to be an efficient catalyst, accelerating the intermolecular ring-closures and leading exclusively to 3,5-disubstituted isoxazoles. The yields of the cycloadducts, however, were influenced by the substituents on the aromatic moiety of the 1,3-dipoles. Moreover, dehydration of the primary products resulted in the corresponding Δ16,17 exo-heterocyclic derivatives. All the synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative effects relative to three human malignant cell lines (HeLa, MCF7 and A2780).",
keywords = "Cycloaddition, Cytotoxic activity, Isoxazoles, Nitrile oxides",
author = "D{\'o}ra Kov{\'a}cs and Zal{\'a}n K{\'a}d{\'a}r and Gerg M{\'o}ty{\'a}n and G. Schneider and J. W{\"o}lfling and I. Zupk{\'o} and E. Frank",
year = "2012",
month = "9",
doi = "10.1016/j.steroids.2012.05.003",
language = "English",
volume = "77",
pages = "1075--1085",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - Synthesis, characterization and biological evaluation of some novel 17-isoxazoles in the estrone series

AU - Kovács, Dóra

AU - Kádár, Zalán

AU - Mótyán, Gerg

AU - Schneider, G.

AU - Wölfling, J.

AU - Zupkó, I.

AU - Frank, E.

PY - 2012/9

Y1 - 2012/9

N2 - Regioselective 1,3-dipolar cycloadditions of different aryl nitrile oxides to mestranol were carried out to furnish novel steroidal 17α-isoxazoles in good to excellent yields. Copper(I) was found to be an efficient catalyst, accelerating the intermolecular ring-closures and leading exclusively to 3,5-disubstituted isoxazoles. The yields of the cycloadducts, however, were influenced by the substituents on the aromatic moiety of the 1,3-dipoles. Moreover, dehydration of the primary products resulted in the corresponding Δ16,17 exo-heterocyclic derivatives. All the synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative effects relative to three human malignant cell lines (HeLa, MCF7 and A2780).

AB - Regioselective 1,3-dipolar cycloadditions of different aryl nitrile oxides to mestranol were carried out to furnish novel steroidal 17α-isoxazoles in good to excellent yields. Copper(I) was found to be an efficient catalyst, accelerating the intermolecular ring-closures and leading exclusively to 3,5-disubstituted isoxazoles. The yields of the cycloadducts, however, were influenced by the substituents on the aromatic moiety of the 1,3-dipoles. Moreover, dehydration of the primary products resulted in the corresponding Δ16,17 exo-heterocyclic derivatives. All the synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative effects relative to three human malignant cell lines (HeLa, MCF7 and A2780).

KW - Cycloaddition

KW - Cytotoxic activity

KW - Isoxazoles

KW - Nitrile oxides

UR - http://www.scopus.com/inward/record.url?scp=84865445982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865445982&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2012.05.003

DO - 10.1016/j.steroids.2012.05.003

M3 - Article

C2 - 22613036

AN - SCOPUS:84865445982

VL - 77

SP - 1075

EP - 1085

JO - Steroids

JF - Steroids

SN - 0039-128X

IS - 11

ER -