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

Article abstract of DOI:10.1016/S0968-0896(97)00106-5

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.