Iminosugars as glucosylceramide processing enzymes inhibitors: design, synthesis and evaluation
This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars.
- Liu, B.
- 13 December 2017
- Thesis in Leiden Repository
This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars. In the studies described, 1-deoxynojirimycin (DNJ), and its known N-alkylated derivatives, served as starting points. DNJ modifications presented here include alteration of the substitution pattern of the piperidine core structure; variation in the N substituent, or a combination of the two. Biological evaluation of the synthesized compounds focused on the glycoprocessing enzymes involved in glucosylceramide metabolism: glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA1) and neutral glucosylceramidase (GBA2), and in all examples presented the inhibitory potency of newly synthesized compounds are compared with that of literature compounds.