1.
Bioorg Med Chem Lett
; 21(9): 2721-4, 2011 May 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-21185185
RESUMO
Amino-anthranilic acid derivatives have been identified as a new class of low serum shifted, high affinity full agonists of the human orphan G-protein-coupled receptor GPR109a with improved ADME properties.
Assuntos
Descoberta de Drogas , Receptores Acoplados a Proteínas G/agonistas , Animais , Flúor/química , Humanos , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Niacina/síntese química , Niacina/química , Niacina/farmacologia , Piridinas/síntese química , Piridinas/química , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos
2.
Bioorg Med Chem Lett
; 18(18): 4963-7, 2008 Sep 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-18760600
RESUMO
A homology model of the nicotinic acid receptor GPR109A was constructed based on the X-ray crystal structure of bovine rhodopsin. An HTS hit was docked into the homology model. Characterization of the binding pocket by a grid-based surface calculation of the docking model suggested that a larger hydrophobic body plus a polar tail would improve interaction between the ligand and the receptor. The designed compounds were synthesized, and showed significantly improved binding affinity and activation of GPR109A.