Arylpropanolamines: selective beta3 agonists arising from strategies to mitigate phase I metabolic transformations.
Bioorg Med Chem Lett
; 17(15): 4290-6, 2007 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-17533126
ABSTRACT
Utilization of N-substituted-4-hydroxy-3-methylsulfonanilidoethanolamines 1 as selective beta(3) agonists is complicated by their propensity to undergo metabolic oxidative N-dealkylation, generating 0.01-2% of a very potent alpha(1) adrenergic agonist 2. A summary of the SAR for this hepatic microsomal conversion precedes presentation of strategies to maintain the advantages of chemotype 1 while mitigating the consequences of N-dealkylation. This effort led to the identification of 4-hydroxy-3-methylsulfonanilidopropanolamines 15 for which the SAR for the unique stereochemical requirements for binding to the beta adrenergic receptors culminated in the identification of the potent, selective beta(3) agonist 15f.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Propanolaminas
/
Agonistas Adrenérgicos beta
/
Agonistas de Receptores Adrenérgicos beta 3
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos