Difluoromethylenated polyhydroxylated pyrrolidines: facile synthesis, crystal structure and biological evaluation

Future Med Chem. 2009 Aug;1(5):991-7. doi: 10.4155/fmc.09.82.

Abstract

In our ongoing program aimed at the design, synthesis and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, the gem-difluoromethylenated polyhydroxylated pyrrolidines as analogues of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP) were designed and prepared. The crystal structure of gem-difluoromethylenated polyhydroxylated pyrrolidine 17 contains an N-H…F intermolecular hydrogen bond. The biological assessment of gem-difluoromethylenated polyhydroxylated pyrrolidines showed that the modification by the gem-difluoromethylene group decreased the inhibitory activities of DMDP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Fluorine / chemistry
  • Hydrogen Bonding
  • Imino Pyranoses / chemistry
  • Mannitol / analogs & derivatives
  • Mannitol / chemistry
  • Molecular Conformation
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacology
  • alpha-Galactosidase / antagonists & inhibitors
  • alpha-Galactosidase / metabolism

Substances

  • 2,5-dideoxy-2,5-imino-D-mannitol
  • Enzyme Inhibitors
  • Imino Pyranoses
  • Pyrrolidines
  • Fluorine
  • Mannitol
  • alpha-Galactosidase