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

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). F...

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Autores principales: Zhou, Xiang, Reilly, Jacqueline E, Loerch, Kathleen A, Hohl, Raymond J, Wiemer, David F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2014
Materias:
Full Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142842/
https://www.ncbi.nlm.nih.gov/pubmed/25161722
http://dx.doi.org/10.3762/bjoc.10.171
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author Zhou, Xiang
Reilly, Jacqueline E
Loerch, Kathleen A
Hohl, Raymond J
Wiemer, David F
author_facet Zhou, Xiang
Reilly, Jacqueline E
Loerch, Kathleen A
Hohl, Raymond J
Wiemer, David F
author_sort Zhou, Xiang
collection PubMed
description 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.
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spelling pubmed-41428422014-08-26 Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase Zhou, Xiang Reilly, Jacqueline E Loerch, Kathleen A Hohl, Raymond J Wiemer, David F Beilstein J Org Chem Full Research Paper 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. Beilstein-Institut 2014-07-18 /pmc/articles/PMC4142842/ /pubmed/25161722 http://dx.doi.org/10.3762/bjoc.10.171 Text en Copyright © 2014, Zhou et al. https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Zhou, Xiang
Reilly, Jacqueline E
Loerch, Kathleen A
Hohl, Raymond J
Wiemer, David F
Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
title Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
title_full Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
title_fullStr Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
title_full_unstemmed Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
title_short Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
title_sort synthesis of isoprenoid bisphosphonate ethers through c–p bond formations: potential inhibitors of geranylgeranyl diphosphate synthase
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142842/
https://www.ncbi.nlm.nih.gov/pubmed/25161722
http://dx.doi.org/10.3762/bjoc.10.171
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