title: The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as α-l-fucosidase inhibitors.
abstract: The ability of a series of pyrrolidines to inhibit several glycosidases was investigated. Using Fleet's 'mirror-image postulate', it was proposed that enantiomeric derivatives of 1,4-dideoxy-1,4-imino-d-lyxitol (a known α-d-galactosidase inhibitor) would show inhibitory activity against α-l-fucosidases. Some modest α-l-fucosidase inhibitory activity was observed for selected compounds (particularly an aminomethyl pyrrolidine) and it was proposed that better activity could be obtained by modifying the C-2 side chain of the pyrrolidine core. The d-galacto carbamate scaffold also exhibited somewhat selective, albeit modest, α-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development.
authors.affiliation: Malaghan Institute of Medical Research, PO Box 7060, Wellington, New Zealand. bstocker@malaghan.org.nz
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Stocker
authors.forename: Seino A K
authors.initials: SA
authors.lastname: Jongkees
authors.forename: Anna L
authors.initials: AL
authors.lastname: Win-Mason
authors.forename: Emma M
authors.initials: EM
authors.lastname: Dangerfield
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
authors.forename: Mattie S M
authors.initials: MS
authors.lastname: Timmer
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D005644:alpha-L-Fucosidase