STRUCTURAL ELUCIDATION AND CONFORMATIONAL PROPERTIES OF THE IMMUNOMODULATOR LINOMIDE

Linomide is a new synthetic immunomodulator which exerts prominent ant i-autoimmune effects in various experimental models. Recently, it was tested in clinical trials to patients suffering from multiple sclerosi s and showed to inhibit the activity of the disease. Therefore, due to its pharmacological importance, we attempted elucidate its structure using one-dimensional and two-dimensional nuclear magnetic resonance ( NMR) techniques and study its conformational properties using a combin ation of two-dimensional NMR spectroscopy and molecular modeling. The conformational analysis of linomide was based on the measurement of in terproton nuclear Overhauser enhancement (NOE) values obtained from a two-dimensional NMR spectrum and a number of molecular modeling techni ques used to calculate the low energy conformers of this compound. Thi s information will serve as an aid to synthetic chemists whom their re search activity is focused on developing linomide analogs with better biological profiles. (C) 1998 Elsevier Science B.V.