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

Abstract

A group of ( Z)-1,1-diphenyl-2-(4-methylsulfonylphenyl)alk-1-enes were synthesized using methodologies that will allow incorporation of a [ 11C]OCH 3 substituent at the para-position of the C-1 phenyl ring, a [ 11C]SO 2CH 3 substituent at the para-position of the C-2 phenyl ring, a [ 18F]OCH 2CH 2F substituent at the para-position of the C-1 phenyl ring, and a [ 18F]CH 2CH 2F 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]OCH 2CH 2F 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.