Effective Labeling of Amine Pharmacophores through the Employment of 2,3-Pyrazinedicarboxylic Anhydride and the Generation of [M(CO)(PyA)P] and -[M(CO)(PyA)P] Complexes (PyA = Pyrazine-2-carboxylate, P = Phosphine, M = Re, Tc).

The -[M(CO)(PyA)(P)] and -[M(CO)(PyA)(P)] neutral complexes (M is Re or Tc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as the bidentate N,O and triphenylphosphine as the monodentate P ligand, are presented. Through the employment of the anhydride of pyrazine-2,3-dicarboxylic acid (PyDA), the PyAH scaffold was conveniently derivatized with the model bioactive amine 1-(2-methoxyphenyl)piperazine, the active part of the 5-HT antagonist WAY100635. Reaction of either PyAH or the pharmacophore-bearing PyAH ligand (LH) with [M(CO)] core in water yielded the intermediate -[M(CO)(PyA)(HO)] complexes. The labile aqua ligand was easily replaced by PPh to yield the -[Re(CO)(PyA)(PPh)] complexes, while in toluene under reflux, the -[Re(CO)(PyA)(PPh)] complexes were obtained. The latter complexes were alternatively obtained from -[Re(CO)(PPh)Cl] by refluxing with the PyA ligand in toluene. The analogous Tc complexes were synthesized quantitatively, showing excellent stability in competition studies. The methodology described herein represents a practical procedure for the effective integration of the -[M(CO)] core with amine-bearing biologically active compounds for diagnosis/therapy.