Synthesis and α-adrenoceptor blocking activity of the enantiomers of benzyl-(2-chloroethyl)-[2-(2-methoxyphenoxy)-1-methylethl]amine hydrochloride Original Research Article

The enantiomers of benzyl-(2-chloroethyl)-[2-(2-methoxyphenoxy)-1-methylethyl]amine hydrochloride (1, CM18) were synthesized and studied pharmacologically for their irreversible antagonism at rat vas deferens α-adrenoceptors. In addition, assignment of the absolute configuration of the two enantiomers of 1 was made by X-ray crystallographic analysis performed on the intermediate amine (+)−2 hydrochloride. The enantiomer (R)-(+)-1 [(R)-(+)-CM18] (a) had a 10-fold preferential blocking activity for α1- versus α2-adrenoceptors, (b) discriminated, like racemic 1, between two possible α1-adrenoceptor subsites/subtypes, with a selectivity ratio of 6.5 and (c) was 10–23 times as potent as the (S)-(−)-enantiomer at α2- and α1-adrenoceptors. Thus, it may be a valuable tool for the characterization of rat vas deferens α1-adrenoceptor subtypes.