Benzofuran- and furan-2-yl-(phenyl)-3-pyridylmethanols: Synthesis and inhibition of P450 aromatase

Saberi, M. R. and Shah, K. and Simons, C. (2005) Benzofuran- and furan-2-yl-(phenyl)-3-pyridylmethanols: Synthesis and inhibition of P450 aromatase. Journal of Enzyme Inhibition and Medicinal Chemistry, 20 (2). pp. 135-141.

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Abstract

A series of benzofuran-2-yl-(phenyl)-3-pyridylmethanol derivatives were prepared using an efficient 1-step procedure in good yields. In addition furan-2-yl-(phenyl)-3-pyridylmethanol derivatives were also prepared to determine the effect of the benzene ring in benzofuran with respect to inhibitory activity. The pyridylmethanol derivatives were all evaluated in vitro for inhibitory activity against aromatase (P450AROM, CYP19), using human placental microsomes. The benzofuran-2-yl-(phenyl)-3-pyridylmethanol derivatives showed good to moderate activity (IC50 = 1.3-25.1 μM), which was either better than or comparable with aminoglutethimide (IC50 = 18.5 μM) but lower than arimidex (IC50 = 0.6 μM), with the 4-methoxyphenyl substituted derivative displaying optimum activity. Molecular modelling of the benzofuran-2-yl-(4-fluorophenyl)-3-pyridylmethanol derivative suggested activity to reside with the (S)-enantiomer. The furan-2-yl-(phenyl)-3-pyridylmethanol derivatives were devoid of activity indicating the essential role of the benzene ring of the benzofuran component for enzyme binding. © 2005 Taylor & Francis Ltd.

Item Type: Article
Additional Information: Cited By :10 Export Date: 16 February 2020 CODEN: JEIMA Correspondence Address: Simons, C.; Medicinal Chemistry Division, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, United Kingdom; email: SimonsC@Cardiff.ac.uk
Uncontrolled Keywords: Benzofuran-2-yl-(phenyl)-3-pyridylmethanols furan-2-yl-(phenyl)-3-pyridylmethanol derivatives Inhibitors Molecular modelling P450 aromatase Proton affinity aminoglutethimide anastrozole aromatase aromatase inhibitor benzofuran 2 yl(2,4 dichlorophenyl) 3 pyridylmethanol benzofuran 2 yl(4 bromophenyl) 3 pyridylmethanol benzofuran 2 yl(4 chlorophenyl) 3 pyridylmethanol benzofuran 2 yl(4 fluorophenyl) 3 pyridylmethanol derivative benzofuran 2 yl(4 iodophenyl) 3 pyridylmethanol benzofuran 2 yl(4 methoxyphenyl) 3 pyridylmethanol benzofuran 2 yl(phenyl) 3 pyridylmethanol derivative benzofuran derivative furan 2 yl(4 chlorophenyl) 3 pyridylmethanol furan 2 yl(4 methoxyphenyl) 3 pyridylmethanol furan 2 yl(phenyl) 3 pyridylmethanol derivative furan derivative unclassified drug article controlled study drug protein binding drug structure drug synthesis enantiomer enzyme inhibition human human cell IC 50 in vitro study microsome molecular model priority journal structure activity relation Aromatase Inhibitors Benzofurans Enzyme Inhibitors Furans Humans Inhibitory Concentration 50 Magnetic Resonance Spectroscopy Methanol Microsomes Models, Chemical Models, Molecular Placenta Protein Binding Protons Software Temperature
Subjects: QU Biochemistry
QV pharmacology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib7 lib7
Date Deposited: 20 Apr 2020 05:01
Last Modified: 20 Apr 2020 05:01
URI: http://eprints.mums.ac.ir/id/eprint/17101

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