Molecular hydropathicity index: Application to a series of allosteric modulators of the M₂ receptors

DFT calculation of four new potential agents muscarinic of bispyridinium type: structure, synthesis, biological activity, hydration, and relations with the potents W84 and DUO-3O

“…The factors contributing to the stabilization of the complex structure include complementarily of shape, H-bonding, and electrostatic and hydrophobic properties. Conformational (superposition) studies of bisammonium (hexamethoniumtype) and bispyridinium (DUO-series) compounds have reported that the main factors affecting the conformation are both: the mutual electrostatic repulsion between the two charged moieties, and the p-p interaction between the two aromatic rings [16]. Thus, two geometrical parameters can be of interest: (1) the distance between the mass centres of the terminal aromatic rings, and (2) the distance between the two formally charged nitrogens [16].…”

“…Calcd. for C 16 Isolated organ technique was carried out (muscle strips of the rat gastric fundus were mounted in organ bath for tension recordings) [29]. Female Whistar rats weighing 150-250 g were used in this study.…”

“…As a consequence of the binding of the alloster to the receptor, the interaction between the ligand and the orthosteric binding site is altered [16]. 2 The orthosteric and allosteric ligand may in a mutual fashion (enhance each other's binding), decrease it, or leave it unaffected, that is, cooperativity is positive, negative or neutral [17][18][19].…”