Synthesis and radiolabelling of a new fluoro anolog of WAY100635: 4-fluoro-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-benzamido]ethyl] piperazine(18F-MPPF)

Aim: The serotonin system in the brain plays an important role and regulates various physiological functions and behavior including depression, anxiety and a lot of kinds of psychotropic syndrome. Among many serotonin receptors , 5HT1A has been fully investigated because of the availability of the best highly selectively 5HT1A agonist 8-OH-DPAT. In order to quantitatively measure the 5HT1A in brain, we reported the synthesis and radiolabelling of fluoro analog of WAY100635 MPPF. Material and Method: MPPF was synthesized using the starting precursor 4-nitro-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-benzamido]ethyl] piperazine. It was obtained by the reaction of an acyl chloride with amino compound. No carrier-added 18F-MPPF can be easily achieved by the nucleophilic method using the starting nitro-precursor in the presence of Kryptofix 222, K2CO3 and DMF. Radiochemical purity(RPC) of 18F-MPPF was determined by HPLC. Results: The physical properties of MPPF and each key intermediate are characterized by IR, 1HNMR, elementary analysis and MS. The radiochemical yield was 10% in 90min using classical heating technique, and was 34% in about 60min using microwave technique. Both the RPC are higher than 98% after being purified on the Sep-Pak isolation. Conclusion: Microwave labelling can enhance the radiochemical yield and shorten the reaction time. Both nitro-precursor and 18F-MPPF have high chemical purities and can be put into preclincal and clinical trials