Development of a Scalable Synthetic Process for DG-051B, A First-in-Class Inhibitior of LTA4H

…, I Kennedy, DW Sullins, W Chen, D Ristic…

Index: Enache, Livia A.; Kennedy, Isaac; Sullins, David W.; Chen, Wei; Ristic, Dragan; Stahl, Glenn L.; Dzekhtser, Sergey; Erickson, Robert A.; Yan, Changren; Muellner, Frank W.; Krohn, Michael D.; Winger, Jennifer; Sandanayaka, Vincent; Singh, Jasbir; Zembower, David E.; Kiselyov, Alex S. Organic Process Research and Development, 2009 , vol. 13, # 6 p. 1177 - 1184

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Citation Number: 11

Abstract

DG-051B is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), currently in Phase II clinical development for the prevention of heart attack. Process optimization led from a linear seven-step synthetic procedure to a convergent four-step manufacturing sequence that has been used to manufacture at 100-kg scale. The entire process can be telescoped due to high conversion reactions, low impurity levels, efficient ...