Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors.
Bioorg Med Chem
; 13(24): 6810-22, 2005 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-16169736
ABSTRACT
Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC50 values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Indometacina
/
Inibidores de Ciclo-Oxigenase
/
Ésteres
/
Ciclo-Oxigenase 2
/
Amidas
/
Indóis
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article