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

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

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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 IC₅₀ 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 IC₅₀ value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.

Original language	English (US)
Pages (from-to)	1645-1650
Number of pages	6
Journal	Beilstein Journal of Organic Chemistry
Volume	10
DOIs	https://doi.org/10.3762/bjoc.10.171
State	Published - Jul 18 2014

All Science Journal Classification (ASJC) codes

Organic Chemistry

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title = "Synthesis of isoprenoid bisphosphonate ethers through C-P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase",

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 IC50 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 IC50 value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.",

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doi = "10.3762/bjoc.10.171",

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T1 - Synthesis of isoprenoid bisphosphonate ethers through C-P bond formations

T2 - Potential inhibitors of geranylgeranyl diphosphate synthase

AU - Zhou, Xiang

AU - Reilly, Jacqueline E.

AU - Loerch, Kathleen A.

AU - Hohl, Raymond J.

AU - Wiemer, David F.

PY - 2014/7/18

Y1 - 2014/7/18

N2 - 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 IC50 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 IC50 value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.

AB - 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 IC50 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 IC50 value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.

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DO - 10.3762/bjoc.10.171

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JO - Beilstein Journal of Organic Chemistry

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

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