Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Bioorg Med Chem Lett. 2010 Sep 1;20(17):5245-50. doi: 10.1016/j.bmcl.2010.06.155. Epub 2010 Jul 23.
A group of (Z)-1,1-diphenyl-2-(4-methylsulfonylphenyl)alk-1-enes were synthesized using methodologies that will allow incorporation of a [(11)C]OCH(3) substituent at the para-position of the C-1 phenyl ring, a [(11)C]SO(2)CH(3) substituent at the para-position of the C-2 phenyl ring, a [(18)F]OCH(2)CH(2)F substituent at the para-position of the C-1 phenyl ring, and a [(18)F]CH(2)CH(2)F substituent at the C-2 position of the olefinic bond. The [(11)C] and [(18)F] 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 [(11)C]OMe or [(18)F]OCH(2)CH(2)F 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.
一组（Z）-1,1-二苯基-2-（4-甲基磺酰基苯基）-1-烯通过使用将[(11)C]OCH(3)取代基引入 C-1 苯基环的对位，将[(11)C]SO(2)CH(3)取代基引入 C-2 苯基环的对位，将[(18)F]OCH(2)CH(2)F 取代基引入 C-1 苯基环的对位，以及将[(18)F]CH(2)CH(2)F 取代基引入烯烃键的 C-2 位的方法合成。这些[(11)C]和[(18)F]放射性示踪剂被设计为潜在的放射性药物，用于在任何 COX-2 上调的器官中成像环加氧酶-2（COX-2）表达。获得的 COX-1/COX-2 抑制数据表明，具有[(11)C]OMe 或[(18)F]OCH(2)CH(2)F 取代基在 C-1 苯基环的对位的化合物可能更适合于成像 COX-2 表达，因为它们能够专一地抑制 COX-2 同工酶。
