Stereoselective action of (R*,R*)-(+/-)-methyl-4-[2-[2-hydroxy-2-(3-chlorophenyl)ethylamino] propyl]-phenoxyacetic acid (BRL37344) on beta-adrenoceptors and metabolic chiral inversion.
Biochem Pharmacol
; 52(10): 1521-7, 1996 Nov 22.
Article
em En
| MEDLINE
| ID: mdl-8937466
ABSTRACT
Stereoisomers of BRL37344 ((R*,R*)-(+/-)-methyl-4-[2-[2-hydroxy-2 -(3-chlorophenyl)ethylamino]propyl]-phenoxyacetic acid), a beta 3-adrenoceptor agonist, were synthesized and separated with good resolution by derivatization with 1-anthroyl cyanide prior to chiral HPLC. Agonist effects on rat right atria, guinea pig trachea, and rat brown adipocytes were due principally to the (RR) isomer, while other isomers (SS, RS, and SR) were much less potent or inactive. Since the racemate (RR +/- SS) was half as potent as the (RR) isomer in all specimens tested, the (SS) isomer does not appear to have antagonistic effects. When [14C](RR)BRL35135A ((R*,R*)-(+/-)-methyl-4-[2-[2-hydroxy-2-(3-chlorophenyl)ethylamino]propy l] -phenoxyacetate hydrobromide), the HBr salt of the methyl ester of BRL37344, was administered orally to male Wistar rats, both the (RR) and (SR) isomers of [14C]BRL37344 were detected in plasma, while only the (SS) isomer of [14C]BRL37344 was detected after [14C](SS)BRL35135A administration. These findings indicate that there is clear stereoselectivity in the effects of BRL37344 on beta-adrenoceptors, and that stereoselective chiral inversion from the RR isomer to the SR isomer occurs in rats.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Receptores Adrenérgicos beta
/
Agonistas Adrenérgicos beta
/
Etanolaminas
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article