1.
Bioorg Med Chem Lett
; 11(12): 1553-6, 2001 Jun 18.
Artigo
em Inglês
| MEDLINE
| ID: mdl-11412979
RESUMO
A novel series of biaryl ether reverse hydroxamate MMP inhibitors has been developed. These compounds are potent MMP-2 inhibitors with limited activity against MMP-1. Select members of this series exhibit excellent pharmacokinetic properties with long elimination half-lives (7 h) and high oral bioavailability (100%).
Assuntos
Ácidos Hidroxâmicos/síntese química , Inibidores de Metaloproteinases de Matriz , Administração Oral , Animais , Antineoplásicos/sangue , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Inibidores Enzimáticos/sangue , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacocinética , Meia-Vida , Ácidos Hidroxâmicos/química , Concentração Inibidora 50 , Injeções Intravenosas , Macaca fascicularis
2.
Bioorg Med Chem Lett
; 11(12): 1557-60, 2001 Jun 18.
Artigo
em Inglês
| MEDLINE
| ID: mdl-11412980
RESUMO
Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable and efficacious in an in vivo model of tumor growth.