The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as ??-l-fucosidase inhibitors

Bridget L. Stocker; Seino A K Jongkees; Anna L. Win-Mason; Emma M. Dangerfield; Stephen G. Withers; Mattie S M Timmer

doi:10.1016/j.carres.2012.11.011

The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as ??-l-fucosidase inhibitors

Bridget L. Stocker, Seino A K Jongkees, Anna L. Win-Mason, Emma M. Dangerfield, Stephen G. Withers, Mattie S M Timmer

Chemical Biology and Drug Discovery

Research output: Contribution to journal › Article › Academic › peer-review

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 ??-d-galactosidase inhibitor) would show inhibitory activity against ??-l-fucosidases. Some modest ??-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, ??-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development. ?? 2012 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	29-32
Number of pages	4
Journal	Carbohydrate Research
Volume	367
DOIs	https://doi.org/10.1016/j.carres.2012.11.011
Publication status	Published - 15 Feb 2013

Keywords

Glycosidase
Inhibitors
Pyrrolidines

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http://www.mendeley.com/research/mirrorimage-postulate-guide-selection-evaluation-pyrrolidines-lfucosidase-inhibitors

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title = "The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as ??-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 ??-d-galactosidase inhibitor) would show inhibitory activity against ??-l-fucosidases. Some modest ??-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, ??-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development. ?? 2012 Elsevier Ltd. All rights reserved.",

keywords = "Glycosidase, Inhibitors, Pyrrolidines",

author = "Stocker, {Bridget L.} and Jongkees, {Seino A K} and Win-Mason, {Anna L.} and Dangerfield, {Emma M.} and Withers, {Stephen G.} and Timmer, {Mattie S M}",

year = "2013",

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doi = "10.1016/j.carres.2012.11.011",

language = "English",

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journal = "Carbohydrate Research",

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T1 - The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as ??-l-fucosidase inhibitors

AU - Stocker, Bridget L.

AU - Jongkees, Seino A K

AU - Win-Mason, Anna L.

AU - Dangerfield, Emma M.

AU - Withers, Stephen G.

AU - Timmer, Mattie S M

PY - 2013/2/15

Y1 - 2013/2/15

N2 - 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 ??-d-galactosidase inhibitor) would show inhibitory activity against ??-l-fucosidases. Some modest ??-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, ??-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development. ?? 2012 Elsevier Ltd. All rights reserved.

AB - 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 ??-d-galactosidase inhibitor) would show inhibitory activity against ??-l-fucosidases. Some modest ??-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, ??-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development. ?? 2012 Elsevier Ltd. All rights reserved.

KW - Glycosidase

KW - Inhibitors

KW - Pyrrolidines

U2 - 10.1016/j.carres.2012.11.011

DO - 10.1016/j.carres.2012.11.011

M3 - Article

C2 - 23295913

SN - 0008-6215

VL - 367

SP - 29

EP - 32

JO - Carbohydrate Research

JF - Carbohydrate Research

ER -

The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as ??-l-fucosidase inhibitors

Abstract

Keywords

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