Synthesis and alpha-adrenoceptor blocking activity of the enantiomers of benzyl-(2-chloroethyl)-[2-(2-methoxyphenoxy)-1-methylethyl]amine hydrochloride.
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 alpha-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 alpha 1-versus alpha 2-adrenoceptors, (b) discriminated, like racemic 1, between two possible alpha 1-adrenoceptor subsites/subtypes, with a selectivity ratio of 6.5 and (c) was 10-23 times as potent as the (S)-(-)-enantiomer at alpha 2- and alpha 1-adrenoceptors. Thus, it may be a valuable tool for the characterization of rat vas deferens alpha 1-adrenoceptor subtypes.
Giardinà
D
D
Department of Chemical Sciences, University of Camerino, Italy. giardina@camserv.unicam.it
Crucianelli
M
M
Marucci
G
G
Angeli
P
P
Melchiorre
C
C
Antolini
L
L
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D051381:Rats; D013237:Stereoisomerism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D001596:Benzylamines; C109262:benzyl-(2-chloroethyl)-(2-(2-methoxyphenoxy)-1-methylethyl)amine