Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors

Daniel B. Goetz, Michelle L. Varney, David F. Wiemer, Sarah A. Holstein

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number115604
JournalBioorganic and Medicinal Chemistry
Volume28
Issue number16
DOIs
StatePublished - Aug 15 2020

Keywords

  • Amide
  • Bioisostere
  • Bisphosphonate
  • Geranylgeranyl diphosphate synthase
  • Inhibition
  • Isoprenoid biosynthesis
  • Myeloma
  • Triazole

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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