title: Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products.
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 (compound1) as a major product, along withN-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.
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, 50-370 Wrocław, Poland. patrycja.miszczyk@pwr.edu.pl.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Miszczyk
authors.affiliation: Faculty of Chemistry, University of Opole, 45-040 Opole, Poland. Dorota.Wieczorek2@uni.opole.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: Department of Inorganic Chemistry, Faculty of Pharmacy, Wrocław Medical University, 50-556 Wrocław, Poland. joanna.galezowska@umed.wroc.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gałęzowska
authors.affiliation: Faculty of Chemistry, University of Opole, 45-040 Opole, Poland. bdziuk@uni.opole.pl.
authors.forename: Błażej
authors.initials: B
authors.lastname: Dziuk
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland. wietrzyk@iitd.pan.wroc.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, 50-370 Wrocław, Poland. ewa.chmielewska@pwr.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Chmielewska
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology; D005561:Formates / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010010:Osteoclasts / Q000187:drug effects; D017905:Phosphites / Q000737:chemistry*; D011199:Potentiometry; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005561:Formates; D017905:Phosphites; D014230:Triazoles; C030544:formic acid
keywords: P-containing drugs; UV-Vis spectroscopy; aminomethylenebisphosponates; anti-proliferative activity; bisphosphonic acids; crystallography; organophosphorus chemistry; osteoclasts; pH-titration; potentiometry; three-component reaction; triazole