Theoretical conformational analysis of some agonists of the H1- and H2-receptors of histamine

Abstract

The conformational equilibrium of β-(aminoethyl)pyridines has been studied by molecular-mechanics using the geometry optimization. It has been determined that the equilibrium is characterized by the nearly statistical distribution of the ap- and sc-conformers about the $$C_{sp^3 } - C_{sp^3 } $$ bond. Substitution of the dimethylamino-group for the amino-group results in a slight shift of the equilibrium toward the ap-rotamers. The global minimum in β-(ammoniumethyl)pyridines corresponds to the conformation with the +sc-orientation about the central C-C bond and the -sc-orientation (in the case of the dimethylammonium derivatives) about the $$C - \mathop N\limits^ + $$ bond. In the latter conformation, the $$H - \mathop N\limits^ + $$ bond of the ammonium group is oriented toward the pyridine cycle. For charged compounds, the regular orthogonal conformation of the aromatic-ring plate is distorted (the vicinal C-C bond becomes eclipsed).