Synthesis and evaluation of morpholino- and pyrrolidinosphingolipids as inhibitors of glucosylceramide synthase.
This paper describes the new synthesis and evaluation of some morpholino- and pyrrolidinosphingolipids and mimics as inhibitors of glucosylceramide synthase. It was found that the pyrrolidino derivatives are generally more active than the morpholino derivatives and the best one was shown to be a nanomolar inhibitor.
Miura
T
T
Frontier Research Program, Institute of Physical and Chemical Research (RIKEN), Saitame, Japan.
Kajimoto
T
T
Jimbo
M
M
Yamagishi
K
K
Inokuchi
J C
JC
Wong
C H
CH
D004341:Drug Evaluation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013107:Sphingolipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009025:Morpholines; D011759:Pyrrolidines; D013107:Sphingolipids; C037574:morpholine; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; C032519:pyrrolidine