Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1377361 | Bioorganic & Medicinal Chemistry Letters | 2008 | 6 Pages |
Abstract
4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3 + 2] cycloaddition of a Münchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and C log P values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
William K.C. Park, Robert M. Kennedy, Scott D. Larsen, Steve Miller, Bruce D. Roth, Yuntao Song, Bruce A. Steinbaugh, Kevin Sun, Bradley D. Tait, Mark C. Kowala, Bharat K. Trivedi, Bruce Auerbach, Valerie Askew, Lisa Dillon, Jeffrey C. Hanselman,