Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases.
Bioorg Med Chem Lett
; 21(18): 5305-9, 2011 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-21807511
ABSTRACT
A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (K(i)=880 nM) and significant selectivity against other human related serine proteases like trypsin (K(i)=729 µM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Tetrazóis
/
Triazóis
/
Inibidores de Serina Proteinase
/
Serina Proteases
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos