The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: the second clinical candidate having a shorter and favorable human half-life.
Bioorg Med Chem Lett
; 20(23): 7159-63, 2010 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-20709553
ABSTRACT
In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t(1/2)=360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34 h.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzopiranos
/
Inibidores de Ciclo-Oxigenase 2
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos