6533b82cfe1ef96bd128ece1

RESEARCH PRODUCT

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products.

Ewa ChmielewskaDorota WieczorekPatrycja MiszczykJoanna WietrzykJoanna GałęzowskaBłażej Dziuk

subject

Models Molecularorganophosphorus chemistryPhosphitesBase (chemistry)FormatesTriazoleMolecular ConformationPharmaceutical ScienceOsteoclastsApoptosis010402 general chemistry01 natural sciencesAnalytical Chemistrylcsh:QD241-441chemistry.chemical_compoundHydrolysisMicelcsh:Organic chemistryCell Line TumorDrug DiscoveryOrganic chemistryAnimals3-Amino-124-triazolePhysical and Theoretical Chemistrycrystallographychemistry.chemical_classificationBone Density Conservation AgentsDiphosphonates010405 organic chemistryChemistryCommunicationOrganic ChemistrySubstrate (chemistry)Triazolesthree-component reactionTriethyl orthoformateUV-Vis spectroscopyMagnetic Resonance Imaging0104 chemical sciencesP-containing drugstriazoleChemistry (miscellaneous)potentiometryaminomethylenebisphosponatesMolecular Medicineanti-proliferative activityAmine gas treatingpH-titrationbisphosphonic acids

description

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.

yearjournalcountryeditionlanguage
2017-02-01Molecules (Basel, Switzerland)
10.3390/molecules22020254https://pubmed.ncbi.nlm.nih.gov/28208725