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

Autor: Goetz DB; Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA., Varney ML; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA., Wiemer DF; Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA; Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA., Holstein SA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: sarah.holstein@unmc.edu.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2020 Aug 15; Vol. 28 (16), pp. 115604. Date of Electronic Publication: 2020 Jun 30.
DOI: 10.1016/j.bmc.2020.115604
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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