Probing for improved selectivity with dipeptide-derived inhibitors of dipeptidyl peptidases 8 and 9: the impact of P1-variation. Issue 3 (26th November 2015)

• Record Type: Journal Article
• Authors: Heirbaut, Leen; van Goethem, Sebastiaan; Jansen, Koen; de Winter, Hans; Lamoen, Nicole; Joossens, Jurgen; Cheng, Jonathan; Chen, Xin; Lambeir, Anne-Marie; de Meester, Ingrid; Augustyns, Koen; van der Veken, Pieter
• Is Part Of: MedChemComm. Volume 7:Issue 3(2016:Mar.)
• Page Start: 433
• Page End: 438
• Publication Date: 2015-11-26
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c5md00454c
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : The influence of P1-variation on DPP8/9 inhibitor selectivity is investigated. Abstract : Selected pyrrolidines, 2-cyanopyrrolidines and heteroaromatic isoindoline analogues were evaluated as P1-residues in dipeptide-derived inhibitors of DPP8/9. Potency testing indicates that DPP8 or DPP9 specificity cannot be obtained with the selected set of P1- and P2-fragments. Nonetheless, the nanomolar DPP8/9 potencies and remarkable selectivities with respect to DPP IV and DPPII, makes inhibitors4c and4h suitable "leads" for future inhibitor optimization effort.