(±)-Sitagliptin-d4 (hydrochloride)

(±)-Sitagliptin-d₄ is intended for use as an internal standard for the quantification of sitagliptin by GC- or LC-MS. Sitagliptin is a mixture of the dipeptidyl peptidase 4 (DPP-4) inhibitor (-)-sitagliptin and (+)-sitagliptin, also known as sitagliptin impurity E, a potential impurity found in commercial preparations of (-)-sitagliptin.¹ (-)-Sitagliptin is a potent inhibitor of DPP-4 (IC₅₀ = 18 nM).² It is selective for DPP-4 over DPP-8 (IC₅₀ = 48 µM) as well as several other peptidases, including DPP-9, DPP-2, and amino peptidase P.^2,3 (-)-Sitagliptin improves glucose tolerance in insulin-resistant Zucker fatty and high-fat diet fed rats as well as ob/ob and high-fat diet fed mice.⁴ It also reduces hyperglycemia in mice fed a high-fat diet with diabetes induced by streptozotocin . Formulations containing (-)-sitagliptin have been used in the treatment of type 2 diabetes mellitus.

1.Kothari, H.M., Dave, M.G., Pandey, B., et al.Process for preparation of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]-triazolo[4,3-α]pyrazin-7(8H)-yl]-L-(2,4,5-trifluorophenyl)butan-2-amine and new impurities in preparation thereof(2013) 2.Biftu, T., Feng, D., Qian, X., et al.(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetesBioorg. Med. Chem. Lett.17(1)49-52(2007) 3.Kim, D., Kowalchick, J.E., Edmondson, S.D., et al.Triazolopiperazine-amides as dipeptidyl peptidase IV inhibitors: Close analogs of JANUVIAT (sitagliptin phosphate)Bioorg. Med. Chem. Lett.17(12)3373-3377(2007) 4.AhrÉn, B.DPP-4 inhibitorsBest Pract.Res.Clin.Endocrinol.Metab.21(4)517-533(2007)