Discovery of a series of indan carboxylic acid glycogen phosphorylase inhibitors
| Autor: | Paul Robert Owen Whittamore, Nidhal Selmi, Andy Stocker, Peter W. Kenny, Stuart Norman Lile Bennett, Adrian Pickup, Andrew D. Campbell, Alleyn T. Plowright, Craig Johnstone, David Whalley, Iain Simpson, Andrew Hancock |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Carboxylic acid
Clinical Biochemistry Carboxylic Acids Biological Availability Pharmaceutical Science Biochemistry Glucagon Glycogen Phosphorylase Liver Form Glycogen phosphorylase In vivo Drug Discovery Glycosyltransferase Animals Humans Hypoglycemic Agents Molecular Biology chemistry.chemical_classification biology Chemistry Organic Chemistry In vitro Rats Rats Zucker Bioavailability Enzyme Indans biology.protein Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:3511-3514 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2010.04.147 |
| Popis: | A series of carboxylic acid glycogen phosphorylase inhibitors, which have potential as oral antidiabetic agents, is described. Defining and applying simple physicochemical design criteria was used to assess the opportunity and to focus synthetic efforts on compounds with the greatest probability of success. The study led to compound 17, which exhibits a good balance of properties including potent inhibition of recombinant human liver glycogen phosphorylase in vitro, a good DMPK profile including excellent bioavailability and low clearance and good in vivo activity in a glucagon challenge model of diabetes in Zucker rats. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect