- Synthesis and biological evaluation of new bisphosphonate-dextran conjugates targeting breast primary tumor
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Bisphosphonates (BPs) have interesting antitumor effects as well in vitro as in vivo, despite their poor bioavailability in the organism after oral ingestion. To overcome this problem and reduce drug doses and secondary effects, we report the chemical synthesis of new bioconjugates. They were built with a nitrogen-containing BP as the drug covalently coupled to the carboxymethyldextran. This polysaccharide was used as a carrier, in order to increase BP lifetime in bloodstream and to target tumor cells which have a strong affinity with dextran. The efficiency of our vectorization system was biologically proved in vitro and in vivo on mammalian carcinoma models in mice.
- Migianu-Griffoni, Evelyne,Chebbi, Imene,Kachbi, Souad,Monteil, Maelle,Sainte-Catherine, Odile,Chaubet, Frederic,Oudar, Olivier,Lecouvey, Marc
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- Analysis of supramolecular interactions in alendroniate alkali metal salts: synthesis, structure, and properties of novel sodium alendronate polymorph
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A new polymorph of anhydrous sodium alendronate, C4H12NO7P2Na, has been synthesized and characterized by single crystal X-ray diffraction as well as infrared spectroscopy and thermal analysis. The title compound crystallizes in the monoclinic P21/c space group. Asymmetric unit consists of one alendronic anion and one sodium cation. An interplay of classical strong O-H…O, N-H…O and non-classical weak C-H…O hydrogen bonds creates 3D framework in the crystal. Contrary to previously reported sodium alendronate salts, in which Na+ cation is surrounded by six-coordinated sphere, in compound (1), the Na+ cation is five-coordinated in a distorted trigonal-bipyramidal geometry. In order to provide a detailed investigation of the molecular arrangement in view of intermolecular interactions, the title compound was compared with alendronic acid and other known alkali metal alendronate salts, retrieved from the Cambridge Crystal Structure Database. The intercontacts were qualitatively and quantitatively compared using Hirshfeld surface analysis. It highlights that strong O…H/H…O and subtle H…H contacts play an influential role in the total surface area. The Me+…H/H…Me+ and Me+…O/O…Me+ contacts are meaningful as well. These evidently simple systems show a diverse complexity. Moreover, the powder X-ray diffraction, DSC, thermogravimetry/derivative thermogravimetry, and FT-IR results are also reported.
- Maniukiewicz, Waldemar,Bojarska, Joanna,Sieroń, Les?aw
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- Investigation of the effect of medium in the preparation of alendronate: till now the best synthesis in the presence of an ionic liquid additive
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The synthesis of the drug alendronate from γ-aminobutyric acid and phosphorus trichloride/phosphorous acid as the P-reagents is revisited using methanesulfonic acid and sulfolane as solvents and ionic liquids (ILs) as additives according to a novel approach. Besides elaborating efficient synthetic methods with a record yield of up to 80%, the misleading literature data were also clarified. It is a novel trend to use ILs as only catalysts or additives and not as solvents.
- Nagy, Dávid Illés,Grün, Alajos,Garadnay, Sándor,Greiner, István,Keglevich, Gy?rgy
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- ORGANIC-INORGANIC HYBRID SOLID HAVING A MODIFIED OUTER SURFACE
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The present invention concerns metal-organic hybrid solids having a modified outer surface. These solids can be used, for example, for the storage and vectoring of molecules of interest such as pharmaceutically active ingredients, compounds of interest in cosmetics and markers, for example contrast agents. These solids have good results in terms of active drug loading capacities, biocompatibility, stability and controlling the release of the active ingredients encapsulated.
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Paragraph 0447; 0448; 0449; 0450; 0451; 0452; 0453
(2015/06/10)
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- The synthesis of risedronic acid and alendronate applying phosphorus oxychloride and phosphorous acid in methanesulfonic acid
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The synthesis of risedronic acid and alendronate from 3-pyridylacetic acid and γ-aminobutyric acid, respectively, using phosphorus oxychloride and phosphorous acid as the P-reagents and methanesulfonic acid as the solvent was optimized, and the role of phosphorus oxychloride and phosphorous acid in the reaction was clarified.
- Grün, Alajos,Kovács, Rita,Garadnay, Sándor,Greiner, István,Keglevich, Gy?rgy
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p. 253 - 258
(2015/04/14)
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- Microwave-assisted efficient synthesis of bisphosphonate libraries: A useful procedure for the preparation of bisphosphonates containing nitrogen and sulfur
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Microwave-assisted rapid and efficient procedure for the synthesis of bisphosphonate and their libraries is described in solvent-free medium. Bisphosphonates having nitrogen and sulfur are synthesized following this new procedure. This procedure is simple and can be useful for the generation of compound libraries of a class of bone-resorptive inhibitors such as N- and N-, S- containing bisphosphonates.
- Lenin, Racha,Raju, Rallabandi Madusudan,Rao, Divvela V. N. Srinivasa,Ray, Uttam Kumar
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p. 1624 - 1629
(2013/07/26)
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- A practical synthesis of alendronate sodium through counterattack reaction
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An efficient synthesis of alendronate sodium, an osteoporosis drug, has been developed through counterattack reaction' involving treatment of the respective acyl phosphonate with (MeO) and TMSBr followed by deblocking with aqueous HCl.
- Seki, Masahiko
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experimental part
p. 1556 - 1558
(2012/07/14)
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- Microwave-assisted synthesis of nitrogen-containing 1- hydroxymethylenebisphosphonate drugs
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A simple, rapid one-pot synthesis of heterocyclic (risedronate, zoledronate) and aminoalkyl (pamidronate, alendronate, neridronate) bisphosphonate drugs using microwave irradiation is presented. Good yields of product are achieved within 20 min, in contrast to conventional synthesis, which typically requires a day or longer.
- Mustafa, Dana A.,Kashemirov, Boris A.,McKenna, Charles E.
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experimental part
p. 2285 - 2287
(2011/05/16)
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- NOVEL PROCESS
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The present invention relates to a process for the preparation of bisphosphonic acids and salts thereof, in particular monosodium salts thereof. The invention also relates to the conversion of the bisphosphonic acids to their sodium salts using an aqueous-organic solvent system. The present invention further relates to the conversion of variable hydrate forms of risedronic acid monosodium salt into a pharmaceutically acceptable hemipentahydrate form by crystallization using an aqueous-organic solvent system.
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Page/Page column 7
(2009/08/16)
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- NOVEL PROCESS FOR THE PREPARATION OF BISPHOSPHONIC ACIDS
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The present invention relates to a process for the preparation of bisphosphonic acids and salts thereof, in particular monosodium salts thereof. The invention also relates to the conversion of the bisphosphonic acids to their sodium salts using an aqueous-organic solvent system. The present invention further relates to the conversion of variable hydrate forms of risedronic acid monosodium salt into a pharmaceutically acceptable hemipentahydrate form by crystallization using an aqueous-organic solvent system.
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Page/Page column 20
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF BISPHOSPHONIC ACID
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The present invention is to relate an improved process using anisole as solvent for the preparation of compound of formula (I) and its pharmaceutically acceptable salts thereof. wherein R represents-NR1R2, or formula (II), a group n = 1,2,3,4 and 5, where R1 and R2 may be same or different and independently represents hydrogen, or C1-6 alkyl;
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Page/Page column 7
(2008/06/13)
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- PROCESS FOR PREPARING BISPHOSPHONIC ACIDS
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A process for preparing a bisphosphonate compound comprises reacting a carboxylic acid with a phosphonating agent, in a cresol solvent.
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Page/Page column 6-7; 7
(2008/06/13)
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- Process for the preparation of biphosphonic acids
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An improved process for bisphosphonylation of acids, substituted acids to obtain compounds with the formula using phosphorus trihalide, phosphorus acid, in presence of phenolic compounds as diluent/solvent.
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Page/Page column 3-4
(2008/06/13)
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- Process for manufacture of 4-amino-hydroxybutylidene-1,1-bisphosphonic acid and its salts
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The preset invention relates to a cost effective, high yielding, reproducible method for the manufacture of alendronic acid or its salt, such as sodium alendronate, from inexpensive and readily available pyrrolidone using phosphonating agents such as PCl3 in the presence of acids such as sulphonic acids, sulphuric acid or phosphoric acid, and pharmaceutical dosage forms of alendronic acid or pharmaceutically acceptable salts thereof.
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Page/Page column 3
(2008/06/13)
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- Improved process for manufacture of 4-amino-hydroxybutylidene-1,1-bisphosphonic acid and its salts
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Disclosed herein is a cost effective, high yielding, reproducible method for the manufacture of alendronic acid or its salt such as sodium alendronate from inexpensive and readily available pyrrolidone using phosphonating agents such as PCl3 in the presence of acids such as sulphonic acids, sulphuric acid or phosphoric acid.
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Page/Page column 5
(2008/06/13)
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- Process for the preparation of bisphosphonic acid
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The present invention is to relate an improved process using anisole as solvent for the preparation of compound of formula (I) and its pharmaceutically acceptable salts thereof. wherein R represents —NR1R2, or a group n=1, 2, 3, 4 and 5, where R1 and R2 may be same or different and independently represents hydrogen, or C1-6 alkyl;
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Page/Page column 2
(2008/06/13)
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- SYNTHESIS OF ALENDRONATE SODIUM TRIHYDRATE
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This invention describes a process for the synthesis of alendronate sodium trihydrate from the reaction of alendronic acid, either anhydrous or in a hydrated state, in an aqueous slurry with sodium hydroxide in water. The pH is adjusted into the range 4.3 - 4.4, the solution is concentrated and the sodium salt thus formed is isolated by crystallization from water.
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Page/Page column 4
(2008/06/13)
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- A PROCESS FOR PREPARATION OF BISPHOSPHONIC ACID COMPOUNDS
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The present invention provides a novel process for preparation of bisphosphonic acids or salts thereof, e.g. alendronic acid, by reacting a carboxylic acid, phosphorous acid and a halophosphorous compound in a water miscible neutral solvent.
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Page/Page column 11
(2008/06/13)
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- α-Amino acid derived bisphosphonates. Synthesis and anti-resorptive activity
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Eleven new bisphosphonates were prepared from naturally-occurring l-amino acids. The synthesis required special attention to amino and side-chain protections. The novel compounds were tested in TPTX (thyroparathyroidectomized) rats against arotinoid-induced hypercalcemia and were compared to alendronate. Most of the compounds showed moderate to no anti-resorptive activity. Two compounds were more active than clodronate, but less than alendronate. Limited SAR conclusions were drawn.
- Mizrahi, Dana M.,Waner, Trevor,Segall, Yoffi
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