- A mild and efficient one-pot synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids. Preparation of new tripod ligands
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A simple and efficient one-pot procedure for synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids by reaction of acyl chlorides and tris(trimethylsilyl)phosphite is described. This method was applied to the synthesis of new phosphonated chelating tripod ligands.
- Lecouvey, Marc,Mallard, Isabelle,Bailly, Théodorine,Burgada, Ramon,Leroux, Yves
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- Cyclodextrins: A promising drug delivery vehicle for bisphosphonate
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Bisphosphonates are well established pharmaceutical drugs with wide applications in medicine. Nevertheless, the side chain and the nature of phosphorous groups could induce a poor aqueous solubility and act on their bioavailability. At the same time, cyclodextrins are cage molecules that facilitate transport of hydrophobic molecules to enhance the intestinal drug absorption of these molecules by forming inclusion complexes. Here we demonstrate that cyclodextrins could be used as a bisphosphonate carrier. The formation of cyclodextrins-bisphosphonate complexes was characterized by 1D and 2D NMR spectroscopy, Isothermal Titration Calorimetry and UV–vis spectroscopy. The results revealed that only the side chain of bisphosphonate was involved in the inclusion phenomenon and its length was a crucial parameter in the control of affinity. Findings from this study suggest that cyclodextrin will be a useful carrier for bisphosphonates.
- Monteil, Maelle,Lecouvey, Marc,Landy, David,Ruellan, Steven,Mallard, Isabelle
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p. 285 - 293
(2016/09/23)
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- METHOD FOR THE SYNTHESIS OF ALKANE-1-HYDROXY-1,1-DIPHOSPHONIC ACID
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The present invention is related to a new method for the synthesis of alkane-1-hydroxy-,1-diphosphonic acid or its salts which includes the steps of -reacting tetraphosphorus hexaoxide and a carboxylic acid under controlled reaction conditions; -hydrolyzing the formed alkane-1-hydroxy-1,1-diphosphonic acid condensates to form alkane-1-hydroxy-1,1-diphosphonic acid; -precipitating the alkane-1-hydroxy-1,1-diphosphonic acid through the use of a suitable solvent; -filtering the alkane-1-hydroxy-1,1-diphosphonic acid and recovering the mother liquor and the suitable solvent.1 The process according to the method of the present invention is highly controllable and is further characterized by a high selectivity.
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Paragraph 0089
(2015/05/06)
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- Bisphosphonates as inhibitors of acid sphingomyelinase
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The present invention refers to bisphosphonate and phosphonate/phosphate compounds of Formulae I and II and its use as inhibitors of aSMase enzyme activity.
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Page/Page column 8-10
(2011/04/14)
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- Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo
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The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC50 50 ~ 4-9 μM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC50 ~ 10-20 μM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pKa values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC50 values 50 values around 1 μM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.
- Ghosh, Subhash,Chan, Julian M. W.,Lea, Christopher R.,Meints, Gary A.,Lewis, Jared C.,Tovian, Zev S.,Flessner, Ryan M.,Loftus, Timothy C.,Bruchhaus, Iris,Kendrick, Howard,Croft, Simon L.,Kemp, Robert G.,Kobayashi, Seike,Nozaki, Tomoyoshi,Oldfield, Eric
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p. 175 - 187
(2007/10/03)
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- PHOSPHONYLATION BY TETRAPHOSPHORUS HEXOXIDE
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The general usefulness of P4O6 as starting material for the preparation of inorganic and organic phosphorus compounds is demonstrated by reactions of P4O6 with nucleophilic and electrophilic compounds.
- Schuelke, Ulrich
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p. 623 - 626
(2007/10/02)
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