Synthesis of N -(3-(4-[ 11 C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1 H -pyrazol-5-yl)pyrazolo[1,5- a ]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation

Abstract

The reference standard N-(3-(4-methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)-3-(piperazin-1-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([C]9) was prepared from its precursor with [C]CHOTf through N-[C]methylation and isolated by HPLC combined with SPE in 50-60% radiochemical yield, based on [C]CO and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol.

Facile synthesis of carbon-11-labeled sEH/PDE4 dual inhibitors as new potential PET agents for imaging of sEH/PDE4 enzymes in neuroinflammation

“…[9][10][11] We are interested in the development of new PET radioligands for neuroinflammation. In our previous work, we have synthesized and developed a series of PET radiotracers [12][13][14][15][16][17][18][19][20] that target the enzyme or receptor for neuroinflammation such as [ 11 Traditionally drugs including PET drugs have been designed based on single-target approach, however, in complex diseases where single-target drugs have failed or show severe limitations, multi-target drugs have emerged as more effective therapeutic approach, since drug molecules often interact with multiple targets. [21][22][23][24] Subsequently, PET radioligand design has benefited from the multitarget approach in drug design and discovery, which opens new avenues to rationally develop next generation of more effective PET agents.…”