Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

Xiang Zhou; Jacqueline E Reilly; Kathleen A Loerch; Raymond J Hohl; David F Wiemer

doi:10.3762/bjoc.10.171

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Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

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Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

Xiang Zhou, Jacqueline E Reilly, Kathleen A Loerch, Raymond J Hohl and David F Wiemer

Beilstein Journal of Organic Chemistry, Vol.10(1), pp.1645-1650

2014

DOI: 10.3762/bjoc.10.171

PMCID: PMC4142842

PMID: 25161722

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Abstract

A set of bisphosphonate ethers has been prepared through sequential phosphonylation and alkylation of monophosphonate ethers. After formation of the corresponding phosphonic acid salts, these compounds were tested for their ability to inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS). Five of the new compounds show IC 50 values of less than 1 μM against GGDPS with little to no activity against the related enzyme farnesyl diphosphate synthase (FDPS). The most active compound displayed an IC 50 value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.

isoprenoid biosynthesis

bisphosphonate

Full Research Paper

Chemistry

organophosphorous

phosphonate formation

Details

Title: Subtitle: Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
Creators: Xiang Zhou - Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242-1294, USA
Jacqueline E Reilly - Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242-1294, USA
Kathleen A Loerch - Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242-1294, USA
Raymond J Hohl - Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242-1294, USA
David F Wiemer - Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242-1294, USA
Resource Type: Journal article
Publication Details: Beilstein Journal of Organic Chemistry, Vol.10(1), pp.1645-1650
DOI: 10.3762/bjoc.10.171
PMID: 25161722
PMCID: PMC4142842
NLM abbreviation: Beilstein J Org Chem
ISSN: 1860-5397
eISSN: 1860-5397
Publisher: Beilstein-Institut
Language: English
Date published: 2014
Academic Unit: Neuroscience and Pharmacology; Chemistry; Internal Medicine
Record Identifier: 9983985956202771

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