Structural Analogues of Selfotel

A small library of phosphonopiperidylcarboxylic adds, analogues of NMDA antagonist selfotel (CGS 19755), was synthesized. First, the series Of aromatic esters was obtained via a palladium-catalyzed cross-coupling reaction (Hirao coupling) of dialkyl phosphites with bromopyridinecarboxylates, followed by-their-hydrolysis. Then, hydrogenation of the resulting Phosphonopyridylcarboxylic acids over PtO2 yielded the desired phosphonopiperidylcarboxylic acid's. NMR studies indicated that the hydrogenation reaction proceeds predominantly by cis addition. Several compounds were obtained as monodystal structures. Preliminary biological studies performed on cultures of neurons suggest that the obtained compounds possess promising activity toward NMDA receptors.