105462-23-5Relevant articles and documents
Optimized synthesis of N-heterocyclic dronic acids; Closing a black-box era
Keglevich, Gy?rgy,Grün, Alajos,Aradi, Klára,Garadnay, Sándor,Greiner, István
, p. 2744 - 2746 (2011)
To clarify the inconsistent patent literature, the synthesis of Zoledronic and Risedronic acids involving a heterocyclic acetic acid (HAA), phosphorous acid (PA) and phosphorus trichloride (PC) as the reagents, and methanesulfonic acid as the solvent was studied in detail. It was found that the best synthesis can be accomplished at 80 °C using HAA and PC in a 1:3.1 molar ratio without any PA.
Novel procedure for the synthesis of 1-hydroxy-1,1-bisphosphonic acids using phenols as medium
Rao, Divvela V. N. Srinivasa,Dandala, Ramesh,Narayanan, Garimella K. A. S. S.,Lenin, Racha,Sivakumaran,Naidu, Andra
, p. 4359 - 4365 (2007)
A facile synthetic route for the synthesis of bisphosphonates in phenols is described. Preparations of some of bisphosphonates, which are presently in clinical use such as risedronic acid and alendronate sodium, are synthesized following this new, simple method. This procedure can be useful for the synthesis of this class of bone-resorptive inhibitors in bulk quantities. Copyright Taylor & Francis Group, LLC.
Microwave-assisted efficient synthesis of bisphosphonate libraries: A useful procedure for the preparation of bisphosphonates containing nitrogen and sulfur
Lenin, Racha,Raju, Rallabandi Madusudan,Rao, Divvela V. N. Srinivasa,Ray, Uttam Kumar
, p. 1624 - 1629 (2013/07/26)
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.
Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo
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
, p. 175 - 187 (2007/10/03)
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.
Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: A potential route to chemotherapy
Martin,Grimley,Lewis,Heath III,Bailey,Kendrick,Yardley,Caldera,Lira,Urbina,Moreno,Docampo,Croft,Oldfield
, p. 909 - 916 (2007/10/03)
We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC50 activity values against parasite replication (e.g. o-risedronate, I50 = 220 nM for T. brucei rhodesiense; risedronate, IC50 = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.
Regimen for treatment or prophylaxis of osteoporosis
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, (2008/06/13)
Methods for treating or preventing osteoporosis, including regimens for intermittent dosing of bone resorption inhibiting polyphosphonate compound or a pharmaceutically acceptable salt or ester of any such compound.
Regimen for treating osteoporosis
-
, (2008/06/13)
A method for treating or preventing osteoporosis utilizing a cyclic regimen comprising alternating for two or more cycles the administration of a bone resorption inhibiting polyphosphonate and a no treatment (rest) period. Further disclosed is a kit for use in implementing this method of treatment.
