Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

Liqiang Chen; Guangyao Gao; Laurent Bonnac; Daniel J. Wilson; Eric M. Bennett; Hiremagalur N. Jayaram; Krzysztof W. Pankiewicz

doi:10.1016/j.bmcl.2007.03.035

Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

Liqiang Chen, Guangyao Gao, Laurent Bonnac, Daniel J. Wilson, Eric M. Bennett, Hiremagalur N. Jayaram, Krzysztof W. Pankiewicz

Center for Drug Design

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

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Abstract

A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration.

Original language	English (US)
Pages (from-to)	3152-3155
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2007.03.035
State	Published - Jun 1 2007

Bibliographical note

Funding Information:
These studies were funded by the Center for Drug Design, University of Minnesota, and USDOD ARMY Grant W81XWH-05-01-0216.

Keywords

IMPDH
Inosine monophosphate dehydrogenase
Methylenebis(sulfonamide)
NAD analogue
Pyrophosphate mimics

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title = "Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor",

abstract = "A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration.",

keywords = "IMPDH, Inosine monophosphate dehydrogenase, Methylenebis(sulfonamide), NAD analogue, Pyrophosphate mimics",

author = "Liqiang Chen and Guangyao Gao and Laurent Bonnac and Wilson, {Daniel J.} and Bennett, {Eric M.} and Jayaram, {Hiremagalur N.} and Pankiewicz, {Krzysztof W.}",

note = "Funding Information: These studies were funded by the Center for Drug Design, University of Minnesota, and USDOD ARMY Grant W81XWH-05-01-0216.",

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AU - Chen, Liqiang

AU - Gao, Guangyao

AU - Bonnac, Laurent

AU - Wilson, Daniel J.

AU - Bennett, Eric M.

AU - Jayaram, Hiremagalur N.

AU - Pankiewicz, Krzysztof W.

N1 - Funding Information: These studies were funded by the Center for Drug Design, University of Minnesota, and USDOD ARMY Grant W81XWH-05-01-0216.

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Y1 - 2007/6/1

N2 - A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration.

AB - A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration.

KW - IMPDH

KW - Inosine monophosphate dehydrogenase

KW - Methylenebis(sulfonamide)

KW - NAD analogue

KW - Pyrophosphate mimics

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ER -

Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

Abstract

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Keywords

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