Phosphorothioate analogs of sn-2 radyl lysophosphatidic acid (LPA): metabolically stabilized LPA receptor agonists.
Bioorg Med Chem Lett
; 23(6): 1865-9, 2013 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-23395664
ABSTRACT
We describe an efficient synthesis of metabolically stabilized sn-2 radyl phosphorothioate analogs of lysophosphatidic acid (LPA), and the determination of the agonist activity of each analog for the six LPA receptors (LPA1-6) using a recently developed TGFα shedding assay. In general, the sn-2 radyl OMPT analogs showed similar agonist activities to the previous 1-oleoyl-2-O-methyl-glycerophosphothioate (sn-1 OMPT) analogs for LPA1-6 receptors. In most cases, the sn-2 radyl-OMPT analogs were more potent agonists than LPA itself. Most importantly, sn-2 alkyl OMPT analogs were very potent LPA5 and LPA6 agonists. The availability of sn-2 radyl OPMT analogs further refines the structure-activity relationships for ligand-receptor interactions for this class of GPCRs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatos
/
Lisofosfolipídeos
/
Receptores de Ácidos Lisofosfatídicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article