X-RAY AND H-1-NMR SPECTROSCOPIC STUDIES OF THE STRUCTURES AND CONFORMATIONS OF THE NEW NOOTROPIC AGENTS RU-35929, RU-47010 AND RU-35965

The crystal and molecular structures of the nootropics (±)1-benzenesulphonyl-2-oxo-5-ethoxypyrrolidine (1), (±)1-(3-pyridinylsulphonyl)-2-oxo-5-ethoxypyrrolidine (2) and (±)1-benzenesulphonyl-2-oxo-5-isopropyloxypyrrolidine (3) have been determined by X-ray analysis. The solution conformation of 1, 2 and 3 has been investigated by 1H NMR spectroscopy. In the solid state, the main feature consists of the similar structural parameters and conformations, with the exception of the conformation adopted by the 5-ethoxy moiety which changes on passing from 1 to 2. The solid state overall enveloped conformation of the 2-pyrrolidinone ring for the three nootropics is found to be retained in solution on the basis of NMR evidence. Comparison between calculated and experimental coupling constant values shows that one of the two possible puckered opposite conformational isomers (half-chair shapes) occurs in solution. The relative pharmacological potencies of 1, 2 and 3 cannot therefore be interpreted in terms of the different conformation features presently detectable by available experimental methods. © 1990.