151. X-Ray, NMR and Theoretical Studies of the structure and Conformation of the Nootropic Agent Tenilsetam
- Author
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Amato, Maria Emanuela, Bandoli, G, Grassi, Antonio, Marletta, A, Nicolini, M, and Perly, B.
- Subjects
Pharmacology ,Chemistry ,Stereochemistry ,Organic Chemistry ,Cyclohexane conformation ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Carbon-13 NMR ,Ring (chemistry) ,Spectral line ,Crystal ,Crystallography ,Molecular geometry ,Drug Discovery ,X-ray crystallography - Abstract
The conformational properties of the nootropic agent Tenilsetam (3-(2-thienyl)-2-piperazinone) have been assessed in the solid, liquid and isolated state by X-ray diffraction, NMR spectroscopy ( 1 H, 13 C) and quantum chemical calculations (MO semi-quantitative PM-3 method), respectively. The thienyl and 2-piperazinone rings are nearly perpendicular in the crystal. The 6-membered ring adopts a very distorted chair conformation with the thienyl at C(6) in equatorial position. Bond angles and distances agree with their standard values. The high-field 1 H and 13 C NMR spectra were run in CDCl 3 solution. The results of the spectral analysis indicate that the 2-piperazinone ring in solution undergoes fast interconversion between the half-chair and the twist-boat forms. Theoretical calculations produced 2 almost equi-energetic conformational minima, both corresponding to the 2 relative possible perpendicular arrangements of the rings. The relative minimum is in fairly good agreement with the conformation in the crystal.
- Published
- 1991