Development of matrix metalloproteinase-13 inhibitors - A structure-activity/structure-property relationship study.
Bioorg Med Chem
; 26(18): 4984-4995, 2018 10 01.
Article
em En
| MEDLINE
| ID: mdl-30249495
ABSTRACT
A structure-activity/structure-property relationship study based on the physicochemical as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhibitor 2, compound 31 was identified which exhibited microsomal half-life higher than 20â¯min, kinetic solubility higher than 20⯵M, and a permeability coefficient greater than 20â¯×â¯10-6â¯cm/s. Compound 31 also showed excellent in vivo PK properties after IV dosing (Cmaxâ¯=â¯56.8⯵M, T1/2 (plasma)â¯=â¯3.0â¯h, Clâ¯=â¯0.23â¯mL/min/kg) and thus is a suitable candidate for in vivo efficacy studies in an OA animal model.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinase 13 da Matriz
/
Inibidores de Metaloproteinases de Matriz
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Áustria