Синтез и антихолинэстеразная активность 2-(диметиламино) этиловых и холиновых эфиров N-замещенных α,β-дегидроаминокислот

A new method for the synthesis tertiary and quaternary amino esters of N-substituted α,β-dehydroamino acids is described. A series of 16 dehydroamino acids esterified to choline or to its ternary analog have been synthesized by the proposed method with a yield of 84 - 93%, and their interactions with human erythrocyte anticholinesterase (ACE) and human plasma butyrylcholinesterase was studied. The IC50 values of the synthesized compounds vary within a broad range (0.16 - 1840 mM). The traditional parameters of the wavefunctions of ligands estimated using the Hartree - Fock method are unable to explain the IC50 variation. The specific properties of molecules, especially in their quaternary ammonium salt forms, are probably related to their structural features, in particular, to the ability of inhibitors to form cyclic conformations (so-called crown structures). Such structures are probably stabilized as a result of the formation of hydrogen bonds between protons of the choline residue and oxygen of the terminal peptide group.