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 | |
| State | Published - Jul 18 2014 |
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All Science Journal Classification (ASJC) codes
- Organic Chemistry
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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; Wiemer, David F.
In: Beilstein Journal of Organic Chemistry, Vol. 10, 18.07.2014, p. 1645-1650.Research output: Contribution to journal › Article
TY - JOUR
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
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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U2 - 10.3762/bjoc.10.171
DO - 10.3762/bjoc.10.171
M3 - Article
VL - 10
SP - 1645
EP - 1650
JO - Beilstein Journal of Organic Chemistry
JF - Beilstein Journal of Organic Chemistry
SN - 1860-5397
ER -