1.
Bioorg Med Chem Lett
; 17(13): 3778-83, 2007 Jul 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-17459706
RESUMO
A novel series of cyclobutenedione centered C(4)-alkyl substituted furanyl analogs was developed as potent CXCR2 and CXCR1 antagonists. Compound 16 exhibits potent inhibitory activities against IL-8 binding to the receptors (CXCR2 Ki=1 nM, IC(50)=1.3 nM; CXCR1 Ki=3 nM, IC(50)=7.3 nM), and demonstrates potent inhibition against both Gro-alpha and IL-8 induced hPMN migration (chemotaxis: CXCR2 IC(50)=0.5 nM, CXCR1 IC(50)=37 nM). In addition, 16 has shown good oral pharmacokinetic profiles in rat, mouse, monkey, and dog.
Assuntos
Química Farmacêutica/métodos , Furanos/química , Furanos/farmacocinética , Receptores de Interleucina-8A/antagonistas & inibidores , Receptores de Interleucina-8B/antagonistas & inibidores , Administração Oral , Animais , Área Sob a Curva , Cães , Desenho de Fármacos , Furanos/síntese química , Humanos , Concentração Inibidora 50 , Interleucina-8/química , Cinética , Camundongos , Ratos
2.
J Antibiot (Tokyo)
; 56(9): 783-6, 2003 Sep.
Artigo
em Inglês
| MEDLINE
| ID: mdl-14632288