ChemMedChem, volume 11, issue 23, pages 2621-2629
Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids
Agnieszka Ambrożak
1
,
Christian Steinebach
1
,
Erin R. Gardner
2
,
Shaunna L. Beedie
3
,
Gregor Schnakenburg
4
,
William D Figg
3
,
2
Clinical Pharmacology Program National Cancer Institute, NIH Bethesda MD 20892 USA
|
3
Molecular Pharmacology Section National Cancer Institute, NIH Bethesda MD 20892 USA
|
Publication type: Journal Article
Publication date: 2016-11-02
Journal:
ChemMedChem
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 3.4
ISSN: 18607179, 18607187
Organic Chemistry
Drug Discovery
Biochemistry
Pharmacology
Molecular Medicine
General Pharmacology, Toxicology and Pharmaceutics
Abstract
The development of novel thalidomide derivatives as immunomodulatory and anti-angiogenic agents has revived over the last two decades. Herein we report the design and synthesis of three chemotypes of barbituric acids derived from the thalidomide structure: phthalimido-, tetrafluorophthalimido-, and tetrafluorobenzamidobarbituric acids. The latter were obtained by a new tandem reaction, including a ring opening and a decarboxylation of the fluorine-activated phthalamic acid intermediates. Thirty compounds of the three chemotypes were evaluated for their anti-angiogenic properties in an ex vivo assay by measuring the decrease in microvessel outgrowth in rat aortic ring explants. Tetrafluorination of the phthalimide moiety in tetrafluorophthalimidobarbituric acids was essential, as all of the nonfluorinated counterparts lost anti-angiogenic activity. An opening of the five-membered ring and the accompanying increased conformational freedom, in case of the corresponding tetrafluorobenzamidobarbituric acids, was well tolerated. Their activity was retained, although their molecular structures differ in torsional flexibility and possible hydrogen-bond networking, as revealed by comparative X-ray crystallographic analyses.
Top-30
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Citations by publishers
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2 publications, 16.67%
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1 publication, 8.33%
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1 publication, 8.33%
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- We do not take into account publications without a DOI.
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Ambrożak A. et al. Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids // ChemMedChem. 2016. Vol. 11. No. 23. pp. 2621-2629.
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Ambrożak A., Steinebach C., Gardner E. R., Beedie S. L., Schnakenburg G., Figg W. D., Gütschow M. Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids // ChemMedChem. 2016. Vol. 11. No. 23. pp. 2621-2629.
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TY - JOUR
DO - 10.1002/cmdc.201600496
UR - https://doi.org/10.1002/cmdc.201600496
TI - Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids
T2 - ChemMedChem
AU - Ambrożak, Agnieszka
AU - Gardner, Erin R.
AU - Beedie, Shaunna L.
AU - Steinebach, Christian
AU - Schnakenburg, Gregor
AU - Figg, William D
AU - Gütschow, Michael
PY - 2016
DA - 2016/11/02 00:00:00
PB - Wiley
SP - 2621-2629
IS - 23
VL - 11
SN - 1860-7179
SN - 1860-7187
ER -
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@article{2016_Ambrożak,
author = {Agnieszka Ambrożak and Erin R. Gardner and Shaunna L. Beedie and Christian Steinebach and Gregor Schnakenburg and William D Figg and Michael Gütschow},
title = {Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids},
journal = {ChemMedChem},
year = {2016},
volume = {11},
publisher = {Wiley},
month = {nov},
url = {https://doi.org/10.1002/cmdc.201600496},
number = {23},
pages = {2621--2629},
doi = {10.1002/cmdc.201600496}
}
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Ambrożak, Agnieszka, et al. “Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids.” ChemMedChem, vol. 11, no. 23, Nov. 2016, pp. 2621-2629. https://doi.org/10.1002/cmdc.201600496.