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

17 Scopus citations

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

Publisher link

10.1016/j.bmcl.2007.03.035

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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.",

year = "2007",

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doi = "10.1016/j.bmcl.2007.03.035",

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TY - JOUR

T1 - Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

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.

PY - 2007/6/1

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

UR - https://www.scopus.com/pages/publications/34247859240

UR - https://www.scopus.com/pages/publications/34247859240#tab=citedBy

U2 - 10.1016/j.bmcl.2007.03.035

DO - 10.1016/j.bmcl.2007.03.035

M3 - Article

C2 - 17395461

AN - SCOPUS:34247859240

SN - 0960-894X

VL - 17

SP - 3152

EP - 3155

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

ER -

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

Abstract

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Keywords

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