کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1395696 | 1501229 | 2006 | 10 صفحه PDF | دانلود رایگان |

A four-point pharmacophore of COX-2 selective inhibitors was derived from a training set of 16 compounds, using the Catalyst program. It consists of a H bond acceptor, two hydrophobic groups and an aromatic ring, in accordance with SAR data of the compounds and with topology of the COX-2 active site. This hypothesis, combined with exclusion volume spheres representing important residues of the COX-2 binding site, was used to virtually screen the Maybridge database. Eight compounds were selected for an in vitro enzymatic assay. Five of them show COX-2 inhibition close to that of nimesulide and rofecoxib, two reference COX-2 selective inhibitors. As a result, structure-based pharmacophore generation was able to identify original lead compounds, inhibiting the COX-2 isoform.
A structure-based four-point pharmacophore of COX-2 selective inhibitors was used to screen the Maybridge database and allowed to identify two original molecules with a new scaffold.Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 41, Issue 12, December 2006, Pages 1446–1455