Cerebral cannabinoid receptor subtype 1 (CB1) is predominantly expressed in the central nervous system, and involved in a variety of brain functions and disorders such as schizophrenia and depression, obesity, drug addiction and alcoholism, and traumatic brain injury. [11C]OMAR ([11C]JHU75528) is a promising radioligand for positron emission tomography (PET) imaging of CB1 receptor, originally developed and characterized at the John Hopkins University. Wishing to study this compound in our PET center, we investigated the synthesis of [11C]OMAR and its analog radioligands by following the literature methods. The published method for the synthesis of OMAR and its analogs, and their corresponding desmethylated precursors gave poor yields. Therefore, alternate synthetic approaches and modifications were studied. OMAR analogs including 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (OMAR), 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-N-(pyrrolidin-1-yl)-1H-pyrazole-3-carboxamide, 1-(2-bromophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, and 1-(2-bromophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(pyrrolidin-1-yl)-1H-pyrazole-3-carboxamide; and their corresponding desmethylated precursors 4-cyano-1-(2,4-dichlorophenyl)-5-(4-hydroxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, 4-cyano-1-(2,4-dichlorophenyl)-5-(4-hydroxyphenyl)-N-(pyrrolidin-1-yl)-1H-pyrazole-3-carboxamide, 1-(2-bromophenyl)-4-cyano-5-(4-hydroxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, and 1-(2-bromophenyl)-4-cyano-5-(4-hydroxyphenyl)-N-(pyrrolidin-1-yl)-1H-pyrazole-3-carboxamide were synthesized from substituted anilines either in 4 and 5 steps with 27-32% and 24-31% yield, or in 3 and 4 steps with 21-30% and 19-28% yield, respectively. [11C]OMAR and its analog radioligands including 4-cyano-1-(2,4-dichlorophenyl)-5-(4-[11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([11C]OMAR), 4-cyano-1-(2,4-dichlorophenyl)-5-(4-[11C]methoxyphenyl)-N-(pyrrolidin-1-yl)-1H-pyrazole-3-carboxamide, 1-(2-bromophenyl)-4-cyano-5-(4-[11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, and 1-(2-bromophenyl)-4-cyano-5-(4-[11C]methoxyphenyl)-N-(pyrrolidin-1-yl)-1H-pyrazole-3-carboxamide  were prepared from their desmethylated precursors with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 50-65% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/�mol specific activity at EOB.

Synthesis of [<sup>11</sup>C]OMAR and its analog radioligands for PET imaging of CB1 receptor in brain diseases

244th National Meeting (2012)

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Synthesis of [11C]OMAR and its analog radioligands for PET imaging of CB1 receptor in brain diseases

Synthesis of [¹¹C]OMAR and its analog radioligands for PET imaging of CB1 receptor in brain diseases