Structure-based design of indole propionic acids as novel PPARalpha/gamma co-agonists.
Bioorg Med Chem Lett
; 16(15): 4016-20, 2006 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-16737814
ABSTRACT
In the quest for novel PPARalpha/gamma co-agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia, we have used a structure-based design approach to identify propionic acids with a 1,5-disubstituted indole scaffold as potent PPARalpha/gamma activators. Compounds 13, 24, and 28 are examples of submicromolar dual agonists with different alpha/gamma EC50 ratios that are selective against the delta-isoform. Analysis of the X-ray complex structure of PPARgamma with the indole propionic acid 13 provides a rationalization for some of the observed SAR.
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Base de dados:
MEDLINE
Assunto principal:
PPAR alfa
/
PPAR gama
/
Indóis
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Suíça