1.
Bioorg Med Chem Lett
; 23(15): 4370-3, 2013 Aug 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-23777782
RESUMO
A series of potent α4ß1/α4ß7 integrin inhibitors is reported, including an inhibitor 12d with remarkable oral exposure and efficacy in rat models of rheumatoid arthritis and Crohn's disease.
Assuntos
Integrina alfa4beta1/antagonistas & inibidores , Integrinas/antagonistas & inibidores , Administração Oral , Animais , Área Sob a Curva , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Modelos Animais de Doenças , Meia-Vida , Humanos , Integrina alfa4beta1/metabolismo , Integrinas/metabolismo , Células Jurkat , Microssomos Hepáticos/metabolismo , Ratos
2.
Bioorg Med Chem Lett
; 23(14): 4117-9, 2013 Jul 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-23743283
RESUMO
Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO2H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats.
