Pharmacophore elucidation of phosphoiodyn A - Potent and selective peroxisome proliferator-activated receptor ß/δ agonists with neuroprotective activity.
Bioorg Med Chem Lett
; 26(8): 1889-93, 2016 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-26988304
ABSTRACT
We report the pharmacophore of the peroxisome proliferator-activated receptor δ (PPARδ) agonist natural product phosphoiodyn A is the phosphonate core. Synthesis of simplified phosphonate esters 13 and 15 provide structurally novel, highly selective and potent PPARδ agonists (EC50=78 and 112 nM, respectively). Further, both compounds demonstrate significant neuroprotective activity in an in vitro cellular model indicating that phosphonates may be an effective novel scaffold for the design of therapeutics for the treatment of neurodegenerative disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
/
Fármacos Neuroprotetores
/
Doenças Neurodegenerativas
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PPAR beta
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PPAR delta
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Poli-Inos
/
Hidrocarbonetos Iodados
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos