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Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors
Journal article   Peer reviewed

Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors

Daniel B Goetz, Michelle L Varney, David F Wiemer and Sarah A Holstein
Bioorganic & medicinal chemistry, Vol.28(16), pp.115604-115604
08/15/2020
DOI: 10.1016/j.bmc.2020.115604
PMCID: PMC7384665
PMID: 32690260
url
https://www.ncbi.nlm.nih.gov/pmc/articles/7384665View
Open Access

Abstract

Geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDPS in enzyme and cell-based assays. The amides were designed as analogues to triazole-based GGDPS inhibitors. Several of the new compounds show GGDPS inhibitory activity in both enzyme and cell assays, with potency dependent on chain length and olefin stereochemistry.
Bisphosphonate Triazole Bioisostere Amide Inhibition Geranylgeranyl diphosphate synthase Myeloma Isoprenoid biosynthesis

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