One of the approaches to the treatment of these diseases is based on inhibition of NMDA-receptors (the drug memantine ), resulting in the suppression of nervous impulses. Transmission of nervous impulses, on the other hand, can be depressed by inhibitory neurotransmitters. Among them are γ-aminobutyric acid (GABA) and glycine. However, GABA itself, due to the low lipophilicity, is poorly transported through the blood-brain barrier, so in medicine they use its structural analogue containing a lipophilic moiety (gabapentin (2-(1-aminocyclohexyl)acetic acid)).
We have proposed to introduce GABA or glycine fragments into compounds containing adamantane skeleton and trifluoromethyl substituent. The proposed structure of the molecules would significantly increase their lipophilicity, and, consequently, penetration through the blood-brain barrier.
The target compounds either structural analogues of GABA (3-amino-5-(trifluoromethyl)adamantane-1-carboxylic acid, 2-(2-amino-5-(trifluoromethyl)adamantan-2-yl)acetic acid), or those of glycine (2-amino-2-(3-(trifluoromethyl)adamantan-1-yl)acetic acid). Currently, we have developed approaches to the synthesis of these compounds and obtained their precursors. It should be noted that the presence of two electron withdrawing groups in the source acid complicates the introduction of the amino group in target compounds.