1.
Bioorg Med Chem Lett
; 13(7): 1277-80, 2003 Apr 07.
Artigo
em Inglês
| MEDLINE
| ID: mdl-12657263
RESUMO
Beginning with the weakly active lead structure 1, a new series of hPPAR agonists was developed. In vivo glucose and triglyceride lowering activity was obtained by homologation and oxamination to 3, then conversion to substituted benzisoxazoles 4 and 5. Further manipulation afforded benzofurans 6 and 7. Compound 7 was of comparable potency as a glucose and triglyceride lowering agent in insulin resistant rodents to BRL 49653.
Assuntos
Hipoglicemiantes/síntese química , Hipoglicemiantes/farmacologia , Fenilacetatos/síntese química , Fenilacetatos/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Tiazolidinedionas , Fatores de Transcrição/agonistas , Animais , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Desenho de Fármacos , Hipoglicemiantes/farmacocinética , Resistência à Insulina , Masculino , Camundongos , Fenilacetatos/farmacocinética , Ratos , Ratos Zucker , Rosiglitazona , Tiazóis/farmacologia , Triglicerídeos/sangue
2.
Bioorg Med Chem Lett
; 13(10): 1801-4, 2003 May 19.
Artigo
em Inglês
| MEDLINE
| ID: mdl-12729668
RESUMO
A series of 5-aryl thiazolidine-2,4-diones containing 4-phenoxyphenyl side chains was designed, synthesized, and evaluated for PPAR agonist activities. One such compound 28 exhibited comparable levels of glucose correction to rosiglitazone in the db/db mouse type 2 diabetes animal model.