Synthesis of (S)-N-Boc-3-hydroxyadamantylglycine a key intermediate of Saxagliptin: Research advances / 国际药学研究杂志

Saxagliptin, a novel antihyperglycemic agent belonging to dipeptidyl peptidase-4 (DPP-4) inhibitor, was developed by Bristol-Myers Squibb and AstraZeneca. It has the merit of obvious hypoglycemic activity, less side effect, good treatment compliance and remarkably high safety, and is widely applied to treatment of type 2 diabetes. In this paper, we review the synthetic methods of the key intermediate (S)-N-Boc-3-hydroxyadamantylglycine (compound 3) as well as its two important compounds 3-hydroxy-1-acetyladamantane (1) and 2-(3-hydroxy-1-adamant-yl)-2-oxoacetic acid (2) and briefly discuss their advantages and disadvantages.

Synthesis and biological activity of substituted xanthines as DPP-IV inhibitors / 药学学报

In order to find more potential DPP-IV inhibitor, a series of xanthine-scaffold analogs of linagliptin, an approved antidiabetes drug, were designed and synthesized for SAR study. All compounds with a concentration of 50 nmol·L-1 showed the inhibitory activity against DPP-IV enzyme in vitro, and the inhibition rate of compounds 1a, 1d and 1f was over 50%. Virtual docking was also performed to facilitate the SAR analysis of these substituted xanthines.