Histamine subtype 3 (H3) receptors are implicated in several neuropsychiatric disorders including sleep disorders, schizophrenia, pain and obesity. Effective radioligands for measuring H3 receptor density in human brain with positron emission tomography (PET) are keenly sought. We previously reported the discovery of the new 18F-labeled ligand [18F]BX-1 (1  , Ki = 0.09 nM, clogD = 2.90) that showed specific binding to H3 receptors in monkey brain and we were interested in developing a 11C-labeled PET radioligand from the same structural class. 2  was selected based on similar properties to those of 1  , namely high affinity (Ki = 0.52 nM), and moderate lipophilicity (clogD = 2.91), plus amenity to 11C-labeling with 11CH3OTf. Labeling precursor 3  was prepared in 5 steps starting from commercially available 4-dianisyl ketone. [11C]2  was obtained by reaction of 3  with 11CH3OTf in the presence of NaH in MeCN in high radiochemical yield (7.5 % based on 11CO2), high radiochemical purity (>98%) and specific activity (5.9 Ci/mmol). Radioligand evaluation is in progress.

Synthesis of a candidate <sup>11</sup>C-labeled brain histamine subtype 3 receptor radioligand for evaluation in monkey

248th National Meeting (2014)

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Synthesis of a candidate 11C-labeled brain histamine subtype 3 receptor radioligand for evaluation in monkey

Synthesis of a candidate ¹¹C-labeled brain histamine subtype 3 receptor radioligand for evaluation in monkey