title: Benzofuran- and furan-2-yl-(phenyl)-3-pyridylmethanols: synthesis and inhibition of P450 aromatase.
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 (P450(AROM), CYP19), using human placental microsomes. The benzofuran-2-yl-(phenyl)-3-pyridylmethanol derivatives showed good to moderate activity (IC50 = 1.3-25.1 microM), which was either better than or comparable with aminoglutethimide (IC50 = 18.5 microM) but lower than arimidex (IC50 = 0.6 microM), 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.
authors.affiliation: Medicinal Chemistry Division, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Saberi
authors.forename: Kajal
authors.initials: K
authors.lastname: Shah
authors.forename: Claire
authors.initials: C
authors.lastname: Simons
mesh_terms: D001141:Aromatase / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry*; D008861:Microsomes / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D010920:Placenta / Q000378:metabolism; D011485:Protein Binding; D011522:Protons; D012984:Software; D013696:Temperature
chemical_list: D047072:Aromatase Inhibitors; D001572:Benzofurans; D004791:Enzyme Inhibitors; D005663:Furans; D011522:Protons; D001141:Aromatase; C105430:benzofuran; C039281:furan; D000432:Methanol