Design, synthesis of celecoxib-tolmetin drug hybrids as selective and potent COX-2 inhibitors.
Bioorg Chem
; 90: 103029, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31212177
ABSTRACT
Three novel series of diarylpyrazole 10b-d and triarylpyrazole derivatives 11a-d &12a-d were synthesized through Vilsmier-Haack condition. The structures of prepared compounds were determined through IR, 1H NMR, 13C NMR, Mass spectral and elemental analysis. Docking of the synthesized compounds over COX-2 active site ensure their selectivity. Moreover, the target compounds were evaluated for both in vitro and in vivo inhibitory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and with excellent anti-inflammatory activity. Compounds 11b, 11d and 12b showed the highest anti-inflammatory activity (67.4%, 62.7%, 61.4% respectively), lower ulcerogenic liability (UIâ¯=â¯2.00, 2.75, 3.25 respectively) than indomethacin (UIâ¯=â¯14) and comparable to celecoxib (UIâ¯=â¯1.75) which were confirmed from the histopatholgical study.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tolmetino
/
Inibidores de Ciclo-Oxigenase 2
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Celecoxib
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Inflamação
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Anti-Inflamatórios
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article