| Title : Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554 - Maezaki_2017_Bioorg.Med.Chem.Lett_27_3565 |
| Author(s) : Maezaki H , Tawada M , Yamashita T , Banno Y , Miyamoto Y , Yamamoto Y , Ikedo K , Kosaka T , Tsubotani S , Tani A , Asakawa T , Suzuki N , Oi S |
| Ref : Bioorganic & Medicinal Chemistry Lett , 27 :3565 , 2017 |
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Abstract :
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. |
| PubMedSearch : Maezaki_2017_Bioorg.Med.Chem.Lett_27_3565 |
| PubMedID: 28579121 |
Maezaki H, Tawada M, Yamashita T, Banno Y, Miyamoto Y, Yamamoto Y, Ikedo K, Kosaka T, Tsubotani S, Tani A, Asakawa T, Suzuki N, Oi S (2017)
Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554
Bioorganic & Medicinal Chemistry Lett
27 :3565
Maezaki H, Tawada M, Yamashita T, Banno Y, Miyamoto Y, Yamamoto Y, Ikedo K, Kosaka T, Tsubotani S, Tani A, Asakawa T, Suzuki N, Oi S (2017)
Bioorganic & Medicinal Chemistry Lett
27 :3565