Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1366715 | Bioorganic & Medicinal Chemistry Letters | 2007 | 5 Pages |
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.
Graphical abstractA series of quinoline-based PDE-10A inhibitors was determined to cause insulin secretion in vitro. Optimized compounds were evaluated in vivo where improvements in glucose tolerance and increases in insulin secretion were measured.Figure optionsDownload full-size imageDownload as PowerPoint slide