105462-24-6Relevant articles and documents
A study on the synthesis of risedronic acid: The role of an ionic liquid additive
Nagy, Dávid Illés,Grün, Alajos,Sinkovicz, Júlia,Garadnay, Sándor,Greiner, István,Keglevich, Gy?rgy
, p. 238 - 244 (2019)
Background: The synthesis of high value risedronic acid is not fully resolved, as, for the time being, the best method based on the preparation from 3-pyridylcarboxylic acid by reaction with phosphorus trichloride in methanesulfonic acid gives risedronic acid in a good yield, but in an unpure form. Methods: Alternative protocols realizing the synthesis in sulfolane as the solvent and/or in the presence of suitable IL additive were developed to obtain the target dronic acid in a pure form. Results & Conclusion: Using phosphorus trichloride and phosphorous acid in two equivalents quantities together with 0.6 equivalents of [bmim][BF4] without any solvent, the method afforded the target dronic acid in a yield of 66% in a pure form.
Potentiating the Anticancer Properties of Bisphosphonates by Nanocomplexation with the Cationic Amphipathic Peptide, RALA
Massey, Ashley S.,Pentlavalli, Sreekanth,Cunningham, Richard,McCrudden, Cian M.,McErlean, Emma M.,Redpath, Philip,Ali, Ahlam A.,Annett, Stephanie,McBride, John W.,McCaffrey, Joanne,Robson, Tracy,Migaud, Marie E.,McCarthy, Helen O.
, p. 1217 - 1228 (2016)
Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs possess anticancer potential, but exploitation of these antiproliferative properties is limited by their toxicities. We previously reported the utility of a cationic amphipathic fusogenic peptide, RALA, to traffic anionic nucleic acids into various cell types in the form of cationic nanoparticles. We hypothesized that complexation with RALA could similarly be used to conceal a BP's hydroxyapatite affinity, and to enhance bioavailability, thereby improving anticancer efficacy. Incubation of RALA with alendronate, etidronate, risedronate, or zoledronate provoked spontaneous electrostatic formation of cationic nanoparticles that did not exceed 100 nm in diameter and that were stable over a range of temperatures and for up to 6 h. The nanoparticles demonstrated a pH responsiveness, possibly indicative of a conformational change, that could facilitate release of the BP cargo in the endosomal environment. RALA/BP nanoparticles were more potent anticancer agents than their free BP counterparts in assays investigating the viability of PC3 prostate cancer and MDA-MB-231 breast cancer cells. Moreover, RALA complexation potentiated the tumor growth delay activity of alendronate in a PC3 xenograft model of prostate cancer. Taken together, these findings further validate the use of BPs as repurposed anticancer agents.
An easy and effective method for synthesis and radiolabelling of risedronate as a model for bone imaging
Motaleb,Adli,El-Tawoosy,Sanad,Abdallah
, p. 157 - 163 (2016)
This study aimed to provide an easy method for synthesis of 1-hydroxy-2-(3-pyridyl) ethylidene bisphosphonic acid monosodium (sod. risedronate) with a high yield of 71%. The synthesized risedronate was labeled with technetium-99 m using two different reducing agents (SnCl2.2H2O and NaBH4) where NaBH4 gave stable complex and higher radiochemical yield more than SnCl2.2H2O. The results showed that, the radiochemical purity of 99mTc(NaBH4)-risedronate was 99.2 ± 0.6% and its stability was up to 6 h. Biodistribution study showed high uptake and long retention of 99mTc(NaBH4)-risedronate in bone starting from 15 min (29 ± 2.5% ID/organ) up to 4 h (35.1 ± 3.2 ID/organ) post injection. This research could introduce an easy and effective method for synthesis and labeling of risedrionate and affording a good tracer for bone imaging.
Microwave-assisted synthesis of nitrogen-containing 1- hydroxymethylenebisphosphonate drugs
Mustafa, Dana A.,Kashemirov, Boris A.,McKenna, Charles E.
, p. 2285 - 2287 (2011)
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.
Environmentally friendly syntheses and tools
Keglevich, Gyoergy,Kovacs, Rita,Gruen, Alajos,Greiner, Istvan
, p. 39 - 41 (2013)
Recent results obtained by our group on MW-assisted reactions, such as the alkylation of PO-functionalized CH-acidic compounds and the addition of dialkyl phosphites to α-ketophosphonates, are summarized together with the rational synthesis of hydroxy-met
The synthesis of risedronic acid and alendronate applying phosphorus oxychloride and phosphorous acid in methanesulfonic acid
Grün, Alajos,Kovács, Rita,Garadnay, Sándor,Greiner, István,Keglevich, Gy?rgy
, p. 253 - 258 (2015)
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.
Rational synthesis of α-hydroxyphosphonic derivatives including dronic acids
Grün, Alajos,Rádai, Zita,S?regi-Nagy, Dávid Illés,Greiner, István,Keglevich, Gy?rgy
, p. 386 - 387 (2019/01/18)
New, green methods have been elaborated for the syntheses of α-hydroxyphosphonates and α-hydroxymethylenebisphosphonic derivatives (HMBPs, dronates). α-Hydroxyphosphonates were prepared via the Pudovik reaction, while the synthesis of HMBPs has been performed in the three-component reaction of carboxylic acids, phosphorus trichloride and phosphorus acid.
A method for preparing sodium
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Paragraph 0023; 0034; 0035, (2017/08/24)
The invention discloses a preparation method of risedronate sodium. The preparation method comprises the following steps of: (1) dissociating 3-pyridinecarboxylicacid chloride in 3-pyridinecarboxylicacid chloride hydrochloride; (2) reacting 3-pyridinecarboxylicacid chloride with diazomethane to generate a diazoketone compound represented by a formula (I); (3) generating 3-pyridylacetic acid under the common action of a catalyst and water; (4) adding hydrochloric acid, separating an organic phase from an inorganic phase, and evaporating and concentrating the inorganic phase to obtain 3-pyridylacetic acid hydrochloride; (5) converting 3-pyridylacetic acid hydrochloride into risedronic acid in the presence of phosphorus trichloride and phosphorous acid; and (6) reacting risedronic acid with sodium hydroxide solution to generate risedronate sodium. The preparation method of risedronate sodium disclosed by the invention has the advantages of being few in reaction step, short in reaction time, simple in post-treatment and higher in product yield.
Methylene bisphosphonates as the inhibitors of HIV RT phosphorolytic activity
Yanvarev,Korovina,Usanov,Khomich,Veps?l?inen,Puljula,Kukhanova,Kochetkov
, p. 153 - 162 (2016/06/13)
The structure-function analysis of 36 methylenebisphosphonates (BPs) as inhibitors of the phosphorolytic activity of native and drug-resistant forms of HIV-1 reverse transcriptase (RT) was performed. It was shown that with the increase of the inhibitory potential of BPs towards the phosphorolytic activity raises their ability to inhibit the RT-catalyzed DNA elongation. Herein, we report the impact of the thymidine analog mutations (TAM) on the activity of bisphosphonates, as well as some structural features of the BPs, allowing them to maintain the inhibitory activity on the enzyme resistant to nucleoside analog therapy. We estimated the Mg2+-coordinating group structure, the linker and the aromatic pharmacophore influence on the inhibitory potential of the BPs. Based on the 31 BPs SAR, several BPs with improved inhibitory properties were designed and synthesized.
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.
