Morozova_1996_Pharm.Chem.J_30_30

By now, a large body of experimental data has been accumulated on the structure of the active surface of acetyicholinesterases and the mechanisms of their inhibition (mostly by organophosphorus compounds). However, compounds of the pyrrolidine group have been insufficiently studied with respect to their antiacetylcholinesterase activity. As is known, the pyrrolidine and dihydropyrimidine fragments enter into the composition of highly-active natural inhibitors of cholinesterases, such as physostigmine and desoxypeganin. We expected that introducing alkyl subsituents at the second carbon atom of pyrrolidine ring would produce some increase in the basicity and anticholinesterase activity of carbamates of pyrrolidine alcohols 9 It was also of interest to study analogous derivatives including a bicyclic fragment with a hexahydropyrimidine ring annelated to the pyrrolidine ring, because these structures contain two nitrogen atoms capable of protonation under the intact organism conditions. In this paper, we present the results on the synthesis and the in vitro anticholinesterase activity of carbamates of 2-al-kyl(phenyl)-N-(o-hydroxyaikyl)pyrrolidines and 9-alkyl-5-(2-hydroxyethyl)-1,5-diazabicyclo[4.3.0]-nonanes.