78285-82-2Relevant academic research and scientific papers
A Bispidol Chelator with a Phosphonate Pendant Arm: Synthesis, Cu(II) Complexation, and 64Cu Labeling
Gillet, Rapha?l,Roux, Amandine,Brandel, Jérémy,Huclier-Markai, Sandrine,Camerel, Franck,Jeannin, Olivier,Nonat, Aline M.,Charbonnière, Lo?c J.
, p. 11738 - 11752 (2017/10/13)
Here we present the synthesis and characterization of a new bispidine (3,7-diazabicyclo[3.3.1]nonane) ligand with N-methanephosphonate substituents (L2). Its physicochemical properties in water, as well as those of the corresponding Cu(II) and Zn(II) complexes, have been evaluated by using UV-visible absorption spectroscopy, potentiometry, 1H and 31P NMR, and cyclic voltammetry. Radiolabeling experiments with 64CuII have been carried out, showing excellent radiolabeling properties. Quantitative complexation was achieved within 60 min under stoichiometric conditions, at room temperature and in the nanomolar concentration range. It was also demonstrated that the complexation occurred below pH 2. Properties have been compared to those of the analogue bispidol bearing a N-methanecarboxylate substituent (L1). Although both systems meet the required criteria to be used as new chelator for 64/67Cu in terms of the kinetics of formation, thermodynamic stability, selectivity for Cu(II), and kinetic inertness regarding redox- or acid-assisted decomplexation processes, substitution of the carboxylic acid function by the phosphonic moiety is responsible for a significant increase in the thermodynamic stability of the Cu(II) complex (+2 log units for pCu) and also leads to an increase in the radiochemical yields with 64CuII which is quantitative for L2.
Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase
Park, Jaeok,Leung, Chun Yuen,Matralis, Alexios N.,Lacbay, Cyrus M.,Tsakos, Michail,Fernandez De Troconiz, Guillermo,Berghuis, Albert M.,Tsantrizos, Youla S.
supporting information, p. 2119 - 2134 (2017/03/17)
The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into nonskeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases. Hit-to-lead optimization of a new series of thienopyrimidine-based monosphosphonates (ThP-MPs) led to the identification of analogs with nanomolar potency in inhibiting hFPPS. Their interactions with the allosteric pocket of the enzyme were characterized by crystallography, and the results provide further insight into the pharmacophore requirements for allosteric inhibition.
Cyclic ketones in spiroannulation
Bjrnstad, Vidar,Undheim, Kjell
experimental part, p. 1793 - 1800 (2009/11/30)
Conversion of a cyclic carbonyl carbon into a quaternary carbon has been effected by a Wittig-Horner reaction with diethyl (N-benzyliden) aminomethylphosphonate and a subsequent alkylation with a protected vinyl ketone. The product was a substrate for spiroannulation after initial hydrolysis. The reaction sequence was carried out as a one-pot reaction. Copyright Taylor & Francis Group, LLC.
