Triaryl (Z)-olefins suitable for radiolabeling with carbon-11 or fluorine-18 radionuclides for positron emission tomography imaging of cyclooxygenase-2 expression in pathological disease

A group of (Z)-1,1-diphenyl-2-(4-methylsulfonylphenyl)alk-1-enes were synthesized using methodologies that will allow incorporation of a [11C]OCH3 substituent at the para-position of the C-1 phenyl ring, a [11C]SO2CH3 substituent at the para-position of the C-2 phenyl ring, a [18F]OCH2CH2F substituent at the para-position of the C-1 phenyl ring, and a [18F]CH2CH2F substituent at the C-2 position of the olefinic bond. The [11C] and [18F] radiotracers are designed as potential radiopharmaceuticals to image cyclooxygenase-2 (COX-2) expression in any organ where COX-2 is upregulated. The COX-1/COX-2 inhibition data acquired suggest that compounds having a [11C]OMe or [18F]OCH2CH2F substituent at the para-position of the C-1 phenyl ring may be more suitable for imaging COX-2 expression in view of their ability to exclusively inhibit the COX-2 isozyme.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide