Synthesis and Biological Investigation of Adamantane Containing Lidocaine Derivative

The synthesis of a novel lidocaine analogue is important, given the extensive range of biological and medicinal activities associated with lidocaine derivatives. Adamantane, a cage saturated hydrocarbon and the smallest diamondoid, is used as a building block to modify the existence drug molecules. Incorporating adamantane is a strategy to improve drug properties such as cell penetration, physicochemical profile, and pharmacokinetic behavior. Accordingly, the novel lidocaine analogue incorporating adamantane was synthesized in two steps. First, ۲,۶-dimethylaniline was acylated with chloroacetyl chloride, followed by nucleophilic substitution with amantadine to yield the adamantane-containing lidocaine analogue. The structure of the molecule was confirmed using ۱H NMR, ۱۳C NMR, and IR spectroscopy. The inhibitory potency of both lidocaine and the modified analogue against trypsin was evaluated. The results show this modification led to a significant increase in the inhibitory potency against trypsin compared to the original lidocaine.

کلیدواژه ها:

Lidocaine ، Diamondoid ، Adamantane ، Trypsin