- Preparation of octaethyl-3-amino-pentane-1,1,5,5-tetrakisphosphonate by catalytic hydrogenation of the corresponding 3-nitro-compound
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The aim of this investigation was to find a convenient synthetical access to tetraethyl-3-amino-1,1-bisphosphonates, a class of chemical compounds which are useful agents in the concept of osteotic vectorisation of antitumor and antiinflammatory drugs. Base-catalyzed addition of nitroalkanes to tetraethylethenylidenebisphosphonate 1 affords the tetraethyl-3-nitro-alkane-1,1-bisphosphonates 3 and 4 and octaethyl-3-nitro-pentane-1,1,5,5-tetrakisphospnonate 2, which can be hydrogenated to the corresponding 3-amino-alkane-1,1-bisphosphonates 6 and 7 and the title compound octaethyl-3-amino-pentane-1,1,5,5-tetrakisphosphonate 5.
- Winckler,Pieper,Keppler
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- Aminoalkylbis(phosphonates): Their complexation properties in solution and in the solid state
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Five geminal bis(phosphonates) containing an amino group in the α, γ or δ position of the carbon chain have been synthesised and their acid-base and complexation properties with Cu2+, Zn2+, Ca2+, Mg2+ and Na+ ions studied by potentiometry. Determination of the stability constants of the complexes with divalent metal ions is complicated by the formation of precipitates. The results of these studies show a negligible effect of the hydroxo group in the α position on the acid-base and complexation properties of the ligands. The presence of an amino group in the α position, however, decreases the basicity, which results in a lower complexation ability of the bis(phosphonates). The crystal structures of the three ligands with different degrees of protonation have also been determined. The structure of the triammonium salt of aminomethylbis(phosphonic acid) shows that the proton is bound to the nitrogen atom in monoprotonated species. The structure of the Cu2+ complex of pamidronate [(Cu2(H2pam) 2}·H2O]n shows the presence of dimeric units with a relatively short distance (2.99 A) between the metal centres. These units form a coordination polymeric chain. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Kubicek, Vojtech,Kotek, Jan,Hermann, Petr,Lukes, Ivan
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- Novel ferrocenylbisphosphonate hybrid compounds: Synthesis, characterization and potent activity against cancer cell lines
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The toxicity of existing anticancer agents on healthy cells and the emergence of multidrug-resistance cancer cells have led to the search for less toxic anticancer agents with different mechanisms of action. In this study, a novel class of ferrocenylbisphosphonate hybrid compounds (H1-H8) were designed and characterized using NMR, IR and HRMS. The in vitro anticancer activity of the hybrid compounds on HeLa (cervix adenocarcinoma) and A549 (non-small cell lung cancer cell lines) was evaluated. The structure–activity relationship of the hybrid molecules was also studied. The lead compound, tetraethyl (3-(4-oxo-4-ferrocenylbutanamido) propane-1-1-diylbis(phosphonate) (H6) exhibited higher cytotoxicity on A549 (IC50 = 28.15 μM) than cisplatin (IC50 = 58.28 μM), while its activity on HeLa cells (IC50 = 14.69 μM) was equivalent to that of cisplatin 15.10 μM (HeLa cells). H6 (IC50 = 95.58 μM) was also five times less toxic than cisplatin (IC50 = 20.86 μM) on fibroblast NIH3T3 suggesting that H6 can be a future replacement for cisplatin due to its non-toxicity to healthy cells. Interestingly, some ferrocene and bisphosphonate parent compounds exhibited promising anticancer activity with 4-ferrocenyl-4-oxobutanoic acid (FI) exhibiting higher cytotoxic activity (IC50 = 1.73 μM) than paclitaxel (IC50 = 3.5 μM) on A549 cell lines. F1 also exhibited lower cytotoxicity than paclitaxel and cisplatin on the normal murine fibroblast cell line (NIH3T3). The molecular docking studies showed H6 strong binding affinity for the STAT3 signaling pathway in A549 cell line, and the MAdCAM-1 and cellular tumor antigen p53 proteins in HeLa cell lines.
- Aderibigbe, Blessing A.,Adeyemi, Samson A.,Anusionwu, Chioma G.,Choonara, Yahya E.,Oselusi, Samson O.,Ubanako, Philemon,Yangkou Mbianda, Xavier
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- Diketopyrrolopyrrole Bis-Phosphonate Conjugate: A New Fluorescent Probe for In Vitro Bone Imaging
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The synthesis of a conjugate molecule between an unusual red-fluorescent diketopyrrolopyrrole (DPP) unit and a bis-phosphonate (BP) precursor by a click-chemistry strategy to target bone tissue and monitor the interaction is reported. After thorough investigation, conjugation through a triazole unit between a γ-azido rather than a β-azido BP and an alkyne-functionalized DPP fluorophore group turned out to be the winning strategy. Visualization of the DPP-BP conjugate on osteoclasts and specific antiresorption activity were successfully demonstrated.
- Chiminazzo, Andrea,Borsato, Giuseppe,Favero, Alessia,Fabbro, Chiara,McKenna, Charles E.,Dalle Carbonare, Luca Giuseppe,Valenti, Maria Teresa,Fabris, Fabrizio,Scarso, Alessandro
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supporting information
p. 3617 - 3626
(2019/02/19)
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- Design of a radiopharmaceutical for the palliation of painful bone metastases: Rhenium-186-labeled bisphosphonate derivative
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To develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we designed a bisphosphonate derivative attached to a stable 186Re- monoaminemonoamidedithiol (MAMA) chela
- Ogawa, Kazuma,Mukai, Takahiro,Arano, Yasushi,Hanaoka, Hirofumi,Hashimoto, Kazuyuki,Nishimura, Hiroshi,Saji, Hideo
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p. 753 - 761
(2007/10/03)
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- A new efficient synthesis of ω-aminoalkylidene-1,1-bisphosphonate tetraethylesters
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Bisphosphonates are interesting therapeutic agents in the management of bone diseases and since several years our laboratory has been developing the chemistry of 1,1-bisphosphonates. This paper describes an original synthesis of two aminoalkylidenebisphosphonates by first preparing the intermediate hydroxyalkylidenebisphosphonates which are transformed into amines via the azides.
- Gourves, Jean-Philippe,Couthon, Helene,Sturtz, Georges
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p. 219 - 229
(2007/10/03)
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