The single-crystal structure of anagliptin, N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methyl pyrazolo[1,5-a]pyrimidine-6-carboxamide, was determined. Two independent molecules were held together by intermolecular hydrogen bonds, and the absolute configuration of the 2-cyanopyrrolidine ring delivered from l-prolinamide was confirmed to be S. The interactions of anagliptin with DPP-4 were clarified by the co-crystal structure solved at 2.85 A resolution. Based on the structure determined by X-ray crystallography, the potency and selectivity of anagliptin were discussed, and an SAR study using anagliptin derivatives was performed.
Watanabe YS, Yasuda Y, Kojima Y, Okada S, Motoyama T, Takahashi R, Oka M (2015) Anagliptin, a potent dipeptidyl peptidase IV inhibitor: its single-crystal structure and enzyme interactions J Enzyme Inhib Med Chem30: 981-8
Watanabe YS, Yasuda Y, Kojima Y, Okada S, Motoyama T, Takahashi R, Oka M (2015) J Enzyme Inhib Med Chem30: 981-8