Synthesis and acid-base and complexing properties of amino-substituted?-hydroxyalkylidenediphosphonic acids

Кабачник, М. И.; Medved, T. Ya.; Dyaglova, N. M.; Polikarpov, Yu. M.; Shcherbakov, B. K.; Bel'skii, F. I.

doi:10.1007/bf00923879

Cited by 12 publications

(7 citation statements)

References 1 publication

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“…Moreover, alendronic acid is very weak by the third dissociation step (Figure 2), and its titration should be problematic. 23,24 At ionic strength 0.1 M KCl and 298.15 K, dissociation constants were estimated as H€ agele et al 25 proved that the increasing distance between the bisphosphonate and the ammonium units (pamidronate f alendronate) leads to a significant increase in pK a1 to pK a4 ; that is, pK a1 is 1.24 for pamidronate (P) and 1.33 for alendronate (A), pK a2 is 1.93 for P and 2.22 for A, pK a3 is 6.04 for P and 6.39 for A, pK a4 is 10.18 for P and 10.96 for A, and pK a5 is 12.14 for P and 11.82 for A at ionic strength 0.1 M and 298.15 K. The last acidity constant, pK a5 , assigned to the NH 3 + f NH 2 deprotonation exhibits, however, the opposite trend, indicating the increasing acidity-modifying interaction of bisphosphonate and amino sites with their decreasing covalent distance.…”

Section: ' Introductionmentioning

confidence: 99%

Thermodynamic Dissociation Constants of Alendronate and Ibandronate by Regression Analysis of Potentiometric Data

et al. 2011

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Mixed dissociation constant(s) of two nitrogen-containing bisphosphonate acids HJL, alendronate and ibandronate, at various ionic strengths I in the range of (0.02 to 0.30) M at (298.15 and 310.15) K have been determined with the use of regression analysis of potentiometric titration data when common parameters pK a,j , J = 1, ..., J, and group parameters L 0 and H T are simultaneously refined. Ibandronate and alendronate are the antiresorptive drugs most widely used to treat osteoporosis owing to their particularly high potency at inhibiting osteoclast-mediated bone resorption. External calibration of the glass electrode cell in the activity scale a H+ was used. The estimate of ill-conditioned group parameters has a great influence on a systematic error in the estimated pK a, and therefore it makes the computational strategy important. As more group parameters are refined and a better fit is achieved, a more reliable estimate of dissociation constants results. The thermodynamic dissociation constant pK a T was estimated by a nonlinear regression of {pK a, I} data and a Debye–Hückel equation. A goodness-of-fit test based on regression diagnostics is the measure of a reliability of parameters and proves that reliable estimates for alendronate pK a2 T = 2.60(1) and 2.76(1), pK a3 T = 6.73(1) and 6.77(1), pK a4 T = 11.51(2) and 11.29(1), and pK a5 T = 12.44(3) and 11.82(3) at (298.15 and 310.15) K, respectively, and for ibandronate pK a2 T = 2.33(1) and 2.50(1), pK a3 T = 6.31(1) and 6.37(1), and pK a4 T = 10.74(1) and 10.65(1) at (298.15 and 310.15) K, respectively, were found.

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Section: ' Introductionmentioning

confidence: 99%

Thermodynamic Dissociation Constants of Alendronate and Ibandronate by Regression Analysis of Potentiometric Data

et al. 2011

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“…Many publications deal with the preparation of alendronate . We have also studied its synthesis starting from γ‐aminobutyric acid (GABA) ( 1 ) in methanesulfonic acid (MSA) as the solvent (Table ; Scheme ).…”

Section: Resultsmentioning

confidence: 99%

“…The temperature was 100°C in each case, while the reaction time was 3 or 4 hour, and the yields were between 18% and 46%. No data were provided on the purities . The synthesis of alendronate was described in a series of other solvents, eg, acetonitrile, n ‐octane, phenol and its derivatives, anisole, benzenesulfonic acid, diphenyl ether, etc.…”

Section: Resultsmentioning

confidence: 99%

Investigation of the effect of medium in the preparation of alendronate: till now the best synthesis in the presence of an ionic liquid additive

et al. 2017

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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.

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“…Reacting β-alanine or GABA with 1.5 equivalents of phosphorus trichloride and 1.5 equivalents of phosphorous acid at 100 °C for 3 h, the yields were in the range of 45%–59% (Table 7/Entries 1 and 3–5) [30,31,32]. Starting from β-alanine or GABA, and measuring in phosphorus trichloride and phosphoric acid in molar equivalents of 2.4:1.5 or 2:3, respectively, the pamidronic acid or alendronic acid was obtained in a yield of 53% and 18%, respectively (Table 7/Entries 2 and 6) [33,34].…”

Section: Synthesis Of Dronic Acid Derivatives In Chlorobenzenementioning

confidence: 99%

Synthesis of Hydroxymethylenebisphosphonic Acid Derivatives in Different Solvents

et al. 2016

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Abstract:The syntheses of hydroxymethylenebisphosphonic acid derivatives (dronic acid derivatives) starting from the corresponding substituted acetic acids and P-reagents, mainly phosphorus trichloride and phosphorous acid are surveyed according to the solvents applied. The nature of the solvent is a critical point due to the heterogeneity of the reaction mixtures. This review sheds light on the optimum choice and ratio of the P-reactants, and on the optimum conditions.

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Synthesis and acid-base and complexing properties of amino-substituted?-hydroxyalkylidenediphosphonic acids

Cited by 12 publications

References 1 publication

Thermodynamic Dissociation Constants of Alendronate and Ibandronate by Regression Analysis of Potentiometric Data

Thermodynamic Dissociation Constants of Alendronate and Ibandronate by Regression Analysis of Potentiometric Data

Investigation of the effect of medium in the preparation of alendronate: till now the best synthesis in the presence of an ionic liquid additive

Synthesis of Hydroxymethylenebisphosphonic Acid Derivatives in Different Solvents

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