Synthesis and characterization of an MRI Gd‐based probe designed to target the translocator protein

摘要: DPA-713 is the lead compound of a recently reported pyrazolo[1,5-a]pyrimidineacetamide series, targeting translocator protein (TSPO 18 kDa), and as such, this structure, well closely related derivatives, have been already successfully used positron emission tomography radioligands. On basis pharmacological core ligands new magnetic resonance imaging probe, coded DPA-C6-(Gd)DOTAMA was designed synthesized in six steps 13% overall yield from DPA-713. The Gd-DOTA monoamide cage (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) represents reporter, which spaced phenylpyrazolo[1,5-a]pyrimidineacetamide moiety (DPA-713 motif) by carbon-atom chain. relaxometric characterization showed typical behavior small-sized molecule (relaxivity value: 6.02 mM−1 s−1 at 20 MHz). good hydrophilicity metal chelate makes soluble water, affecting thus its biodistribution with respect to parent lipophilic molecule. For reason, it deemed interest load probe large carrier order increase residence lifetime blood. Whereas binds serum albumin low affinity constant, can be entrapped into liposomes (both membrane inner aqueous cavity). stability supramolecular adduct formed Gd-complex assessed competition test albumin. Copyright © 2013 John Wiley & Sons, Ltd.