|
|||||
|
|
Inhibitors of dipeptidyl peptidase 8 and dipeptidyl peptidase 9. Part 1: identification of dipeptide derived leads |
|
| Authors: | Van der Veken Pieter De Meester Ingrid Dubois Véronique Soroka Anna Van Goethem Sebastiaan Maes Marie-Berthe Brandt Inger Lambeir Anne-Marie Chen Xin Haemers Achiel Scharpé Simon Augustyns Koen |
| Institution: | aDepartment of Medicinal Chemistry, University of Antwerp (UA), Universiteitsplein 1, B-2610 Antwerp, Belgium;bMedical Biochemistry, University of Antwerp (UA), Universiteitsplein 1, B-2610 Antwerp, Belgium;cDivision of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhu Nan, Miaoli 350, Taiwan, ROC |
| Abstract: | Dipeptide derivatives bearing various P2 residues and pyrrolidine derivatives as P1 mimics were evaluated in order to identify lead structures for the development of DPP8 and DPP9 inhibitors. Structure–activity-relationship data obtained in this way led to the preparation of a series of α-aminoacyl ((2S, 4S)-4-azido-2-cyanopyrrolidines). These compounds were shown to be nanomolar DPP8/9 inhibitors with modest overall selectivity toward DPP IV and DPP II. |
| Keywords: | DPP8 DPP9 DPP IV DPP4 DPP II DPP2 Inhibitors Selectivity Dipeptide-derived Cyanopyrrolidines Nitriles |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |