| Title : 1-((3S,4S)-4-amino-1-(4-substituted-1,3,5-triazin-2-yl) pyrrolidin-3-yl)-5,5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes - Andrews_2011_Bioorg.Med.Chem.Lett_21_1810 |
| Author(s) : Andrews KM , Beebe DA , Benbow JW , Boyer DA , Doran SD , Hui Y , Liu S , McPherson RK , Neagu C , Parker JC , Piotrowski DW , Schneider SR , Treadway JL , VanVolkenberg MA , Zembrowski WJ |
| Ref : Bioorganic & Medicinal Chemistry Lett , 21 :1810 , 2011 |
|
Abstract :
A 3-amino-4-substituted pyrrolidine series of dipeptidyl peptidase IV (DPP-4) inhibitors was rapidly developed into a candidate series by identification of a polar valerolactam replacement for the lipophilic 2,4,5-trifluorophenyl pharmacophore. The addition of a gem-difluoro substituent to the lactam improved overall DPP-4 inhibition and an efficient asymmetric route to 3,4-diaminopyrrolidines was developed. Advanced profiling of a subset of analogs identified 5o with an acceptable human DPP-4 inhibition profile based on a rat PK/PD model and a projected human dose that was suitable for clinical development. |
| PubMedSearch : Andrews_2011_Bioorg.Med.Chem.Lett_21_1810 |
| PubMedID: 21324688 |
Andrews KM, Beebe DA, Benbow JW, Boyer DA, Doran SD, Hui Y, Liu S, McPherson RK, Neagu C, Parker JC, Piotrowski DW, Schneider SR, Treadway JL, VanVolkenberg MA, Zembrowski WJ (2011)
1-((3S,4S)-4-amino-1-(4-substituted-1,3,5-triazin-2-yl) pyrrolidin-3-yl)-5,5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes
Bioorganic & Medicinal Chemistry Lett
21 :1810
Andrews KM, Beebe DA, Benbow JW, Boyer DA, Doran SD, Hui Y, Liu S, McPherson RK, Neagu C, Parker JC, Piotrowski DW, Schneider SR, Treadway JL, VanVolkenberg MA, Zembrowski WJ (2011)
Bioorganic & Medicinal Chemistry Lett
21 :1810