1.
Bioorg Med Chem Lett
; 17(10): 2869-73, 2007 May 15.
Article
in English
| MEDLINE
| ID: mdl-17400452
ABSTRACT
Modulation of cAMP levels has been linked to insulin secretion in preclinical animal models and in humans. The high expression of PDE-10A in pancreatic islets suggested that inhibition of this enzyme may provide the necessary modulation to elicit increased insulin secretion. Using an HTS approach, we have identified quinoline-based PDE-10A inhibitors as insulin secretagogues in vitro. Optimized compounds were evaluated in vivo where improvements in glucose tolerance and increases in insulin secretion were measured.
Subject(s)
Insulin/metabolism , Islets of Langerhans/drug effects , Phosphodiesterase Inhibitors/pharmacology , Phosphoric Diester Hydrolases/metabolism , Quinolines/pharmacology , Drug Design , Humans , Insulin Secretion , Islets of Langerhans/metabolism , Molecular Structure , Phosphodiesterase Inhibitors/chemical synthesis , Phosphoric Diester Hydrolases/drug effects , Quinolines/chemical synthesis , Quinolines/chemistry , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 16(2): 297-301, 2006 Jan 15.
Article
in English
| MEDLINE
| ID: mdl-16275080
ABSTRACT
A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes.