Reaction of 3-amino-1,2,4-triazole with diethyl phosphite and triethyl orthoformate: Acid-base properties and antiosteoporotic activities of the products

Patrycja Miszczyk, Dorota Wieczorek, Joanna Gałeȩzowska, Błazej Dziuk, Joanna Wietrzyk, Ewa Chmielewska, Diego Muñoz-Torrero, Rodolfo Lavilla, Christopher Hulme

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction-namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.

Original languageEnglish (US)
Article number254
JournalMolecules
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2017

Keywords

  • Aminomethylenebisphosponates
  • Anti-proliferative activity
  • Bisphosphonic acids
  • Crystallography
  • Organophosphorus chemistry
  • Osteoclasts
  • P-containing drugs
  • PH-titration
  • Potentiometry
  • Three-component reaction
  • Triazole
  • UV-Vis spectroscopy

ASJC Scopus subject areas

  • Medicine(all)
  • Organic Chemistry

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    Miszczyk, P., Wieczorek, D., Gałeȩzowska, J., Dziuk, B., Wietrzyk, J., Chmielewska, E., Muñoz-Torrero, D., Lavilla, R., & Hulme, C. (2017). Reaction of 3-amino-1,2,4-triazole with diethyl phosphite and triethyl orthoformate: Acid-base properties and antiosteoporotic activities of the products. Molecules, 22(2), [254]. https://doi.org/10.3390/molecules22020254