| Title : Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting DPP-4 Inhibitors for the Treatment of Type 2 Diabetes - Zhang_2020_J.Med.Chem_63_7108 |
| Author(s) : Zhang C , Ye F , Wang J , He P , Lei M , Huang L , Huang A , Tang P , Lin H , Liao Y , Liang Y , Ni J , Yan P |
| Ref : Journal of Medicinal Chemistry , 63 :7108 , 2020 |
| Abstract : In the present work, a novel series of trifluoromethyl-substituted tetrahydropyran derivatives were rationally designed and synthesized as potent DPP-4 inhibitors with significantly improved duration time of action over current commercially available DPP-4 inhibitors. The incorporation of the trifluoromethyl group on the 6-position of the tetrahydropyran ring of omarigliptin with the configuration of (2R,3S,5R,6S) not only significantly improves the overall pharmacokinetic profiles in mice but also maintains comparable DPP-4 inhibition activities. Further preclinical development of compound 2 exhibited its extraordinary efficacy in vivo and good safety profile. Clinical studies of compound 2 (Haisco HSK7653) are now ongoing in China, which revealed that inhibitor 2 could serve as an efficient candidate with a once-biweekly therapeutic regimen. |
| ESTHER : Zhang_2020_J.Med.Chem_63_7108 |
| PubMedSearch : Zhang_2020_J.Med.Chem_63_7108 |
| PubMedID: 32452679 |
Zhang C, Ye F, Wang J, He P, Lei M, Huang L, Huang A, Tang P, Lin H, Liao Y, Liang Y, Ni J, Yan P (2020)
Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting DPP-4 Inhibitors for the Treatment of Type 2 Diabetes
Journal of Medicinal Chemistry
63 :7108
Zhang C, Ye F, Wang J, He P, Lei M, Huang L, Huang A, Tang P, Lin H, Liao Y, Liang Y, Ni J, Yan P (2020)
Journal of Medicinal Chemistry
63 :7108