- Al(OH)3 facilitated synthesis of water-soluble, magnetic, radiolabelled and fluorescent hydroxyapatite nanoparticles
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Magnetic and fluorescent hydroxyapatite nanoparticles were synthesised using Al(OH)3-stabilised MnFe2O4 or Fe3O4 nanoparticles as precursors. They were readily and efficiently radiolabelled with 18F. Bisphosphonate polyethylene glycol polymers were utilised to endow the nanoparticles with excellent colloidal stability in water and to incorporate cyclam for high affinity labelling with 64Cu.
- Cui,Green,Blower,Zhou,Yan,Zhang,Djanashvili,Mathe,Veres,Szigeti
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Read Online
- New approaches towards the synthesis of 1,2,3,4-tetrahydro isoquinoline-3-phosphonic acid (TicP)
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Two new strategies for the efficient synthesis of racemic 1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (TicP) (±)-2 have been developed. The first strategy involves the electron-transfer reduction of the easily obtained α,β-dehydro phosphonophenylalanine followed by a Pictet–Spengler cyclization. The second strategy involves a radical decarboxylation–phosphorylation reaction on 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). In both strategies, the highly electrophilic N-acyliminium ion is formed as a key intermediate, and the target compound is obtained in good yield using mild reaction conditions and readily available starting materials, complementing existing methodologies and contributing to the easy accessibility of (±)-2 for further research.
- Viveros-Ceballos, José Luis,Matías-Valdez, Lizeth A.,Sayago, Francisco J.,Cativiela, Carlos,Ordó?ez, Mario
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p. 451 - 459
(2021/03/06)
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- 1-Aminovinylphosphonate Esters as Substrates for the Diels-Alder Reaction: First Synthetic and Theoretical Study
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The Diels-Alder reaction of 1-aminovinylphosphonate esters has been studied for the first time as a suitable procedure leading to quaternary carbocyclic α-aminophosphonates. The reaction is influenced by steric effects at the phosphonate functionality (bulky groups hinder the reaction) and electronic effects at the amino group (electron-withdrawing substituents increase the reaction rate). The exo/endo ratio is constant, and no influence of the solvent is observed. The experimental results have been rationalized by DFT methods.
- Jiménez-Andreu, M. Mercedes,Bueno-Morón, Jorge,Sayago, Francisco J.,Cativiela, Carlos,Tejero, Tomás,Merino, Pedro
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supporting information
p. 1268 - 1272
(2019/01/24)
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- Syntheses and evaluation of 68Ga- and 153Sm-labeled DOTA-conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases
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This article reports the syntheses and evaluation of 68Ga- and 153Sm-complexes of a new DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-conjugated geminal bisphosphonate, DOTA-Bn-SCN-BP, for their potential uses in the early detection of skeletal metastases by imaging and palliation of pain arising from skeletal metastases, respectively. The conjugate was synthesized in high purity following an easily adaptable three-step reaction scheme. Gallium-68- and 153Sm-complexes were prepared in high yield (>98%) and showed excellent in vitro stability in phosphate-buffered saline (PBS) and human serum. Both the complexes showed high affinity for hydroxyapatite particles in in vitro binding study. In biodistribution studies carried out in normal Wistar rats, both the complexes exhibited rapid skeletal accumulation with almost no retention in any other major organ. The newly synthesized molecule DOTA-Bn-SCN-BP would therefore be a promising targeting ligand for the development of radiopharmaceuticals for both imaging skeletal metastases and palliation of pain arising out of it in patients with cancer when radiolabeled with 68Ga and 153Sm, respectively. A systematic comparative evaluation, however, showed that there was no significant improvement of skeletal accumulation of the 153Sm-DOTA-Bn-SCN-BP complex over 153Sm-DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid) as the later itself demonstrated optimal properties required for an agent for bone pain palliation.
- Chakraborty, Sudipta,Goswami, Dibakar,Chakravarty, Rubel,Mohammed, Sahiralam Khan,Sarma, Haladhar Deb,Dash, Ashutosh
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p. 1618 - 1626
(2018/06/04)
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- COMPOUND FOR BONE SCANNING AND USE THEREOF
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The disclosure provides a compound comprising bisphosphonate functional group and chelating agent. The bisphosphonate functional group part has high affinity for bone tissue, and the chelating agent part has high affinity for metal tracer such as radioisotope. The disclosed compound could be rapidly adsorbed onto the bone surface, and could steady emit ionizing radiation. Therefore, the disclosed compound is suitable for bone scanning technology to find abnormalities in bone.
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Paragraph 0056
(2016/11/07)
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- A bisphosphonate for 19F-magnetic resonance imaging
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19F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate (19F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow 19F resonance and a bisphosphonate group that may be used for labelling inorganic materials based in calcium phosphates and metal oxides. The potential of 19F-BP to provide contrast was analysed in vitro and in vivo using 19F-MRI. In vitro studies demonstrated the potential of 19F-BP as an MRI contrast agent in the millimolar concentration range with signal-to-noise ratios (SNR) comparable to previously reported fluorinated probes. The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of 19F-BP, showing uptake in the liver and in the bladder/urinary system areas. However, bone uptake was not observed. In addition, 19F-BP showed undesirable toxicity effects in mice that prevent further studies with this compound at the required concentrations for MRI contrast. This study highlights the importance of developing 19F MRI probes with the highest signal intensity achievable. " 2016 The Authors.
- Kenny, Gavin D.,Shaw, Karen P.,Sivachelvam, Saranja,White, Andrew J.P.,Botnar, Rene M.,De Rosales, Rafael T.M.
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- Synthesis, characterization, and antibacterial properties of a hydroxyapatite adhesive block copolymer
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A novel diblock copolymer composed of bisphosphonate and pyridine oligomers has been prepared by reversible addition-fragmentation transfer (RAFT) polymerization. Ag ion was introduced into the polymer via its coordination with the pyridine groups, followed by a reduction process to obtain Ag nanoparticles with diameters of 5-15 nm measured by transmission electron microscopy (TEM). In addition, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) proved successful introduction of Ag nanoparticles into polymer. Ag nanoparticles containing polymer exhibited excellent antibacterial properties toward Lactobacillus plantarum (L. plantarum). In order to investigate its practical application as an antibacterial coating, the synthesized polymer was tethered onto hydroxyapatite (HA, main mineral component of natural bone, teeth, and most of implants for bone repair) surfaces via interaction between the polymers bisphosphonate group and HA, forming ~4 nm thick layers. Ag nanoparticles (5-15 nm in diameter) uniformly distributed around the HA particles were fabricated following the above process. The ability of the coating to kill the bacteria L. plantarum was determined, which revealed strong antibacterial properties.
- Zhang, Qiang Matthew,Serpe, Michael J.
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p. 8018 - 8025
(2015/02/19)
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- PHOSPHONATED RIFAMYCINS AND USES THEREOF FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS
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The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.
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Page/Page column 75
(2011/11/06)
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- PHOSPHONATED RIFAMYCINS AND USES THEREOF FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS
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The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.
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Page/Page column 151-152
(2010/04/03)
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- PHOSPHONATED GLYCOPEPTIDE AND LIPOGLYCOPEPTIDE ANTIBIOTICS AND USES THEREOF FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS
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The present invention is directed to antimicrobial compounds which have an affinity for binding bones. More particularly, the invention is directed to phosphonated derivatives of glycopeptide or lipoglycopeptide antibiotics. These compounds are useful as antibiotics for the prevention or treatment of bone and joint infections, especially for the prevention and treatment of osteomyelitis.
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- Phosphonated Fluoroquinolones, Antibacterial Analogs Thereof, and Methods for the Prevention and Treatment of Bone and Joint Infections
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The present invention relates to phosphonated fluoroquinolones, antibacterial analogs thereof, and methods of using such compounds. These compounds are useful as antibiotics for prevention and/or the treatment of bone and joint infections, especially for the prevention and/or treatment of osteomyelitis.
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Page/Page column 64
(2008/12/09)
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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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p. 333 - 344
(2007/10/03)
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- A bisphosphonate monoamide analogue of DOTA: A potential agent for bone targeting
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A new macrocyclic DOTA-like ligand (BPAMD) for bone imaging and therapy containing a monoamide bis(phosphonic acid) bone-seeking group was designed and synthesized. Its lanthanide(III) complexes were prepared and characterized by 1H and 31P NMR spectroscopy. The Gd(III)-BPAMD complex was investigated in detail by 1H and 17O relaxometric studies to inspect parameters relevant for its potential application as an MRI contrast agent. Sorption experiments were conducted with Gd(III) and Tb(III) complexes using hydroxyapatite (HA) as a model of bone surface. Very effective uptake of the Gd-BPAMD complex by the HA surface was observed in NMR experiments. Radiochemical studies with the (160Tb-BPAMD)-HA system proved the sorption to be remarkably fast and strong on one hand and fully reversible on the other hand. The strong (Gd-BPAMD)-HA interaction was also supported by 1H NMRD measurements in the presence of a hydroxyapatite slurry, which showed an increase of the rotational correlation time upon adsorption of the complex on the HA surface, resulting in a significant relaxivity enhancement. The amide-bis(phosphonate) moiety is the only factor responsible for the binding of the complex to HA.
- Kubicek, Vojtech,Rudovsky, Jakub,Kotek, Jan,Hermann, Petr,Elst, Luce Vander,Muller, Robert N.,Kolar, Zvonimir I.,Wolterbeek, Hubert Th.,Peters, Joop A.,Lukes, Ivan
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p. 16477 - 16485
(2007/10/03)
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- Synthesis of aminobisphosphonate
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A new facile synthesis of aminobisphosphonate was reported. Dibenzylamine bisphosphonate (1) is prepared from dibenzylamine, triethyl orthoformate and diethyl phosphite. Deprotection by hydrogen transfer reaction and acid hydrolysis afforded aminobisphosphonate (2).
- Kantoci, Darko,Kane Denike,Wechter, William J.
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p. 2037 - 2043
(2007/10/03)
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- Guanidinoalkyl-1,1-bisphosphonic acid derivatives, process for their preparation and their use
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The invention describes tautomeric compounds of the formula Ia, Ib or Ic STR1 and/or their physiologically tolerable salts, in which R1, R2, R3, R4, R5, R6 and R7 are a hydrogen atom, substituted (C1 -C7)-alkyl, (C3 -C10)-cycloalkyl, substituted phenyl or (C1 -C4)-alkylphenyl, R2 is substituted phosphoric acid, R2 and R3, R2 and R5 or R4 and R5 form a monocyclic 5- to 7-membered saturated or unsaturated heterocyclic ring which is mono- or polysubstituted, R8, R9, R10 and R11 are a hydrogen atom or (C1 -C5)-alkyl, X is a hydrogen atom, hydroxyl or halogen, l and n are an integer from 0 to 7, m is an integer from 0 to 2, and the sum of the numbers l, m and n is less than or equal to 10, a process for the preparation of the compounds of the formula Ia, Ib or Ic, pharmaceuticals and their use for the prophylaxis or treatment of osteoporosis.
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- ORGANISCHE PHOSPHORVERBINDUNGEN 75. Herstellung und Eigenschaften von Aminomethylendiphosphinaten und -diphosphonaten, RR1NCH2(OR3>2 und Derivaten
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Substituted aminomethylene-bis(phosphinates) are obtained in good yield by the interaction of substituted aminomethylenedichlorides with phosphonites or from the three component reaction consisting of a primary amine, orthoformates and the half-esters of phosphonous acids. 3-Methylpyridyl-2-aminomethylene-bis(O-ethyl-methylphosphinate) hydrolizes easily in water to give the corresponding acid in which neither of the nitrogen atoms is protonated, .Amino- and alkylamino-methylene-bis(phosphonates) are obtained, in high yield, by the hydrogenolytic debenzylation of the corresponding benzyl-derivatives, using Pd/C as a catalyst.Aminomethylene-bis(phosphonate), H2NCH2 (7) is a water-clear liquid which can be molecularly distilled, b.p. 125-127 deg/0.1 Torr., 31P +20.28 ppm, JPCH 20.5 Hz.On prolonged standing at 20 deg C it forms slowly a half-ester. 7 gives the typical reactions of a primary amine.Thus on treatment with dimethylformamid-dimethylacetal it yields a formamidine 10, with isocyanates it forms urea derivatives e.g. 11 and 12, and with aldehydes Schiff's bases are produced e.g. 13 to 18.The latter can be hydrogenated using Pt/C as catalyst to give monosubstituted aminomethylenediphosphonates e.g. 23 and 24.However on hydrogenation of 18 over Pt/C 7 was obtained.Thus 2-pyrrylmethyl represents a new, with H2/Pt/C, cleavageable group when bound to nitrogen.Acylation of 7 yields the corresponding acyl-derivatives, e.g. 19 and 20, and interaction with cyanamide produces guanidinomethylene-diphosphonate 21.
- Maier, Ludwig
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p. 311 - 322
(2007/10/02)
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