96464-20-9Relevant academic research and scientific papers
Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554
Maezaki, Hironobu,Tawada, Michiko,Yamashita, Tohru,Banno, Yoshihiro,Miyamoto, Yasufumi,Yamamoto, Yoshio,Ikedo, Koji,Kosaka, Takuo,Tsubotani, Shigetoshi,Tani, Akiyoshi,Asakawa, Tomoko,Suzuki, Nobuhiro,Oi, Satoru
supporting information, p. 3565 - 3571 (2017/07/07)
We report a design strategy to obtain potent DPP-4 inhibitors by incorporating salt bridge formation with Lys554 in the S1′ pocket. By applying the strategy to the previously identified templates, quinoline 4 and pyridines 16a, 16b, and 17 have been identified as subnanomolar or nanomolar inhibitors of human DPP-4. Docking studies suggested that a hydrophobic interaction with Tyr547 as well as the salt bridge interaction is important for the extremely high potency. The design strategy would be useful to explore a novel design for DPP-4 inhibitors having a distinct structure with a unique binding mode.
