Bicyclic isoureas derived from 1-deoxynojirimycin are potent inhibitors of β-glucocerebrosidase.
A series of bicyclic isourea derivatives were prepared from 1-deoxynojirimycin using a concise synthetic protocol proceeding via a guanidino intermediate. Inhibition assays with a panel of glycosidases revealed that these deoxynojirimycin-derived bicyclic isoureas display very potent inhibition against human recombinant β-glucocerebrosidase with IC50 values in the low nanomolar range.
Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. n.i.martin@uu.nl.
Alen
A
Sevšek
Maša
M
Čelan
Bibi
B
Erjavec
Linda
L
Quarles van Ufford
Javier
J
Sastre Toraño
Ed E
EE
Moret
Roland J
RJ
Pieters
Nathaniel I
NI
Martin
D017485:1-Deoxynojirimycin / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D014510:Urease / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; D005962:Glucosylceramidase; D014510:Urease