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Trelagliptin succinate, a novel once-weekly oral dipeptidyl peptidase-4 (DPP-4) inhibitor, was approved for the Japanese market on March 26, 2015
Trelagliptin exhibited a better potency against human DPP-4 than alogliptin and sitagliptin, along with its excellent selectivity and slow-binding properties that may partially contribute to its sustained efficacy. In phase III clinical studies, once-weekly oral trelagliptin provided long-term safety and efficacy in both monotherapy and combination with other antidiabetic medicines and was proved to be noninferior to its analogue alogliptin used once daily.
2-({6-[(3R)-3-Aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)-4-fluorobenzonitrile Monosuccinate (1)
Synthesis of Trelagliptin Succinate
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, Qun Hao, Hongyan Li, Zhenren Liu, and Weicheng Zhou*
An improved process for the synthesis of antidiabetic drug trelagliptin succinate through unprotected (R)-3-aminopiperidine was described. The impurity profile with different conditions of the key substitution was illustrated, and then the best reaction condition was identified. The optimizations also included the bromination of 4-fluoro-2-methylbenzonitrile so that the process became efficient and concise.
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