ORGN 471 |
Process development of PPAR-gamma dominant agonist LY519818
| John R. Rizzo, Tony Y. Zhang, Samuel R. Wendel, Chauncey D. Jones, and Robert W. Towsley. Chemical Process Research and Development, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4813, Indianapolis, IN 46285 |
| LY 519818 is a Peroxisome Proliferator Activated Receptor (PPAR) gamma dominant agonist currently undergoing studies for Type II diabetes mellitus. This presentation will describe the strategic route selection and the process development efforts to prepare LY 519818. The evolution of an efficient manufacturing process to prepare clinical trial material will be discussed. Several enantioselective syntheses, including those featuring the application of an immobilized enzyme catalyzed kinetic resolution and asymmetric reduction, will be analyzed with regard to their suitability for large-scale commercial manufacturing. The final process is only four steps, and features low solvent volumes, minimal processing times, crystalline intermediates and operational simplicity.  |
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