Work

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

Year: 2014

Type: article

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.

Source: Beilstein Journal of Organic Chemistry

DOI: 10.3762/bjoc.10.171

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

Institution: University of Iowa

Language: English

Topic: Organophosphorus compounds synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: diamond

Funders: Roy J. Carver Charitable Trust, National Institutes of Health, National Institute of General Medical Sciences

Award: Predoctoral Training in the Pharmacological Sciences