OMS-210

5-HT(3) receptor is an attractive target for the development of therapeutic agents for use in brain, heart and cancer diseases, and imaging agents for use in biomedical imaging technique PET. Benzoxazole derivatives are a novel class of 5-HT(3) receptor partial agonists with high binding affinity. Carbon-11 labeled benzoxazole derivatives have been synthesized as new potential PET radioligands for imaging 5-HT(3) receptor. The target tracers were prepared by N-[(11)C]methylation of their corresponding precursors using [(11)C]CH(3)OTf and isolated by HPLC purification procedure in 40-50% radiochemical yields, which were decay corrected to the end of bombardment (EOB), based on [(11)C]CO(2). The overall synthesis time was 20-25min from EOB. The radiochemical purity was >99%, and specific activity was in a range of 74-111 GBq/micromol at the end of synthesis (EOS).

During our search for therapeutic agents to treat diarrhea-predominant IBS, we found that 2-substituted benzoxazole derivatives have a characteristic 5-HT(3) receptor partial agonist activity with high affinity. Some of these compounds showed high in vitro metabolical stability, and 6g showed marked antidiarrhetic activity with little side effect of constipation in in vivo tests. Our results indicate that 5-HT(3) receptor partial agonists might be superior as therapeutic agents to the drugs currently used for IBS treatment.