Alendronic acid CAS 66376-36-1
Introduction：Basic information about Alendronic acid CAS 66376-36-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Alendronic acid Basic information
| Product Name: | Alendronic acid |
| Synonyms: | 4-AMINO-1-HYDROXY-1,1-BUTYLIDINEDIPHOSPHONIC ACID;(4-AMINO-1-HYDROXY-1-PHOSPHONOBUTYL)PHOSPHONIC ACID;(4-AMINO-1-HYDROXYBUTYLIDENE)-BIS-(PHOSPHONIC ACID);(4-AMINO-1-HYDROXYBUTYLIDENE)DIPHOSPHONIC ACID;ALENDRONATE;ALENDRONIC ACID;(4-amino-1-hydroxybutylidene)bis-phosphonicaci;4-amino-1-hydroxybutylidene-1,1-bis(phosphonicacid) |
| CAS: | 66376-36-1 |
| MF: | C4H13NO7P2 |
| MW: | 249.1 |
| EINECS: | 204-352-8 |
| Product Categories: | Miscellaneous Biochemicals;(intermediate of alendronate sodium) |
| Mol File: | 66376-36-1.mol |
Alendronic acid Chemical Properties
| Melting point | 230-235°C |
| Boiling point | 616.7±65.0 °C(Predicted) |
| density | 1.857±0.06 g/cm3(Predicted) |
| storage temp. | Store at -20°C |
| Water Solubility | Insoluble in water |
| solubility | Aqueous Base (Sparingly), Methanol (Slightly), Water (Very Slightly) |
| pka | pK1 2.72 ±0.05; pK2 8.73 ±0.05; pK3 10.5 ±0.1; pK4 11.6 ±0.1 at 25°, (0.1M KCl) |
| form | powder to crystal |
| color | White to Light yellow |
| Merck | 14,229 |
| Stability: | Hygroscopic |
| EPA Substance Registry System | Phosphonic acid, P,P'-(4-amino-1-hydroxybutylidene)bis- (66376-36-1) |
Safety Information
| RIDADR | 1759 |
| RTECS | SZ6521833 |
| HS Code | 2931.90.9051 |
| HazardClass | 8 |
| PackingGroup | III |
| Hazardous Substances Data | 66376-36-1(Hazardous Substances Data) |
| Chemical Properties | White to Light yellow powder to crystal. |
| Originator | Adronat ,Neopharmed ,Italy |
| Uses | Alendronate acid is an inhibitor of FDPS. |
| Preparation | Synthesis of Alendronic Acid: 1 mol of 4-aminobutyric acid was added to 1.5 mol of molten phosphoric acid at 95°C, followed by dropwise addition of 2 mol of phosphorus trihalide over 60 minutes. After the reaction mixture hardened, heating was continued for an additional 3 hours. The mixture was then hydrolyzed by adding 300 mL of water. Following cooling, the solution was poured into 1500 mL of methanol, and the resulting precipitate was collected to yield alendronic acid in 64.6% yield. |
| Definition | ChEBI: Alendronic acid is a 1,1-bis(phosphonic acid) that is methanebis(phosphonic acid) in which the two methylene hydrogens are replaced by hydroxy and 3-aminopropyl groups. It has a role as an EC 2.5.1.1 (dimethylallyltranstransferase) inhibitor and a bone density conservation agent. It is a 1,1-bis(phosphonic acid) and a primary amino compound. It is a conjugate acid of an alendronate(1-). |
| Indications | Alendronic acid is a bisphosphonate used to treat and prevent osteoporosis and corticosteroid-induced osteoporosis. |
| Manufacturing Process | 4-Amino-1-hydroxybutylidene-1,1-diphosphonic acid (ABDT). Orthosphophorous acid (102.7 g; 1.25 moles) is introduced into a 2 liter-flaskwith condenser, stirrer and dropping funnel, placed on a thermostatized bath;the air is then removed with a nitrogen stream which is continued during allthe reaction. The acid is melted by heating the bath to 95°C. When melting iscomplete, 4-aminobutyric acid (103.3; 1 mole) is added under stirring whichis continued till obtaining a doughy fluid. Phosphorous trihalide (176 ml; 2moles) is added dropwise causing the mixture to boil and evolution of gaseoushydrochloric acid which is damped by means of a suitable trap. The additionrate is adjusted so as to keep a constant reflux for about 60 minutes. Whenthe addition is nearly over, the mixture swells, slowly hardening. Stirring iscontinued as long as possible, whereafter the mixture is heated for further 3hours. Without cooling, but removing the bath, water (300 ml) is added, firstslowly and then quickly. Heating and stirring are started again. Decolorizingcharcoal is added and the mixture is boiled for about 5 minutes, then hotfilteredon paper and the filtrate is refluxed for 6 hours. After cooling is slowlypoured in stirred methanol (1500 ml) causing thereby the separation of awhite solid which collected and dried (161 g; 64.6%). The structure of ABDTis confirmed by IR spectrum, proton magnetic and nuclear magneticresonance spectrum and elemental analysis. The sodium salt of this acid may be prepared by adding of equivalent ofsodium hydroxide. |
| Therapeutic Function | Antiosteoporotic |
| Hazard | A reproductive hazard. |
| Clinical Use | Bisphosphonate: Treatment and prophylaxis of osteoporosis |
| Drug interactions | Potentially hazardous interactions with other drugs Calcium salts: reduced absorption of alendronate. |
| Metabolism | Alendronate transiently distributes to soft tissues but is then rapidly redistributed to bone or excreted in the urine. There is no evidence that alendronate is metabolised in animals or humans. Following a single intravenous dose of [14C]-alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the faeces. |
| References | [1] DÁVID ILLÉS NAGY. Synthesis of Hydroxymethylenebisphosphonic Acid Derivatives in Different Solvents.[J]. Molecules, 2016, 21 8. DOI:10.3390/molecules21081046. [2] E. A. VOLOSNIKOVA. The synthesis of TNF-alpha conjugates with alendronic acid[J]. Russian Journal of Bioorganic Chemistry, 2017, 42 6: 638-645. DOI:10.1134/S1068162016060145. [3] MOHAMED F. MADY* Malcolm A K Rocio Ortega. Exploring Modified Alendronic Acid as a New Inhibitor for Calcium-Based Oilfield Scales[J]. Energy & Fuels, 2022, 36 4: 1863-1873. DOI:10.1021/acs.energyfuels.1c03936. |
Alendronic acid Preparation Products And Raw materials
| Raw materials | Phosphoric acid-->4-Aminobutyric acid-->Phosphorus trichloride-->Orthophosphorus acid |
