The results of a comprehensive structure-affinity relationship study on the effect of the quaternization (i.e., N-methylation) of structurally different ligands in the classes of tropane and quinuclidine derivatives are described. This study shows that the effects of the quaternization of the basic nitrogen of these 5-HT3 receptor ligands appear to be strictly structure-dependent suggesting that different binding modes are operative at 5-HT3 receptor binding site. The different effect of the quaternization of the basic nitrogen of structurally different ligands were rationalized in tern-is of the interaction with the receptor by means of the combined use of experimental techniques (X-ray diffraction and NMR studies) and computational simulation studies. (C) 2002 Elsevier Science Ltd. All rights reserved.
Novel potent 5-HT3 receptor ligands based on the pyrrolidone structure. Effects of the quaternization of the basic nitrogen on the interaction with 5-HT3 receptor / A., Cappelli; A., Gallelli; C., Braile; M., Anzini; S., Vomero; L., Mennuni; F., Makovec; Menziani, Maria Cristina; DE BENEDETTI, Pier Giuseppe; A., Donati; G., Giorgi. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 10:8(2002), pp. 2681-2691. [10.1016/S0968-0896(02)00093-7]