| Literature DB >> 17400452 |
Louis-David Cantin1, Steven Magnuson, David Gunn, Nicole Barucci, Marina Breuhaus, William H Bullock, Jennifer Burke, Thomas H Claus, Michelle Daly, Lynn Decarr, Ann Gore-Willse, Helana Hoover-Litty, Ellalahewage S Kumarasinghe, Yaxin Li, Sidney X Liang, James N Livingston, Timothy Lowinger, Margit Macdougall, Herbert O Ogutu, Alan Olague, Ronda Ott-Morgan, Robert W Schoenleber, Adrian Tersteegen, Philip Wickens, Zhonghua Zhang, Jian Zhu, Lei Zhu, Laurel J Sweet.
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.Entities:
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Year: 2007 PMID： 17400452 DOI： 10.1016/j.bmcl.2007.02.061
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823