Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors.

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.

journal_name

Bioorg Med Chem

authors

Goetz DB,Varney ML,Wiemer DF,Holstein SA

doi

10.1016/j.bmc.2020.115604

subject

Has Abstract

pub_date

2020-08-15 00:00:00

pages

115604

issue

16

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(20)30434-X

journal_volume

28

pub_type

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