text: Researchers at BI discovered that using a buty-2-nyl group resulted in a potent candidate, called BI-1356 (Figure 10). In 2008 BI-1356 was undergoing phase III clinical trials; it was released as linagliptin in May 2011. X-ray crystallography has shown that that xanthine type binds the DPP-4 complex in a different way than other inhibitors:
  1. The amino group also interacts with the Glu205, Glu206 and Tyr662
  2. The buty-2-nyl group occupies the S1-pocket
  3. The uracil group undergoes a π-stacking interaction with the Tyr547 residue
  4. The quinazoline group undergoes a π-stacking interaction with the Trp629 residue