New aminocyclitols as modulators of glucosylceramide metabolism.
A series of 13 aminocyclitol derivatives belonging to two different families is described. Their configuration is governed by the regio- and stereocontrolled epoxide opening of a suitably protected conduritol-B epoxide. Studies on several glycosyl processing enzymes indicate that some of them are good inhibitors of glucosylceramide hydrolase. A rationale to account for preliminary structure-activity relationships is provided.
Egido-Gabás
Meritxell
M
Research Unit on Bioactive Molecules (RUBAM), Department de Química Orgànica Biológica, Institut d'Investigaciones Quimiques i Ambientals de Barcelona (IIQAB-C.S.I.C), Jordi Girona 18-26, 08034, Barcelona, Spain.
Serrano
Pedro
P
Casas
Josefina
J
Llebaria
Amadeu
A
Delgado
Antonio
A
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005963:Glucosylceramides / Q000378:metabolism*; D006595:Hexosamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007294:Inositol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009904:Optical Rotation; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005963:Glucosylceramides; D006595:Hexosamines; D007294:Inositol; D005959:Glucosidases; C011423:conduritol epoxide