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Alendronate sodium structure
Alendronate sodium structure

Alendronate sodium

Iupac Name:sodium;(4-amino-1-hydroxy-1-phosphonobutyl)-hydroxyphosphinate;trihydrate
CAS No.: 121268-17-5
Molecular Weight:325.122
Modify Date.: 2023-08-02 04:11
Introduction: A bisphosphonate used as a bone reabsoption inhibitor View more+
1. Names and Identifiers
1.1 Name
Alendronate sodium
1.2 Synonyms

(4-Amino-1-hydroxy-1,1-butanediyl)bis(phosphonic acid) trihydrate (4-Amino-1-hydroxy-1-phosphonobutyl)phosphonic Acid Monosodium Salt Trihydrate 4-amino-1-hydroxy-1-phosphonobutyl phosphonic acid, monosodium, MK-217 4-amino-1-hydroxy-1-phosphonobutyl phosphonic acid,monosodium MK-217 4-amino-1-hydroxy-1-phosphonobutyl phosphonic acid,monosodium,Alendronate sodium trihydrate Adronat Alendronate trihydrate sodium Alendronate (sodium hydrate) Alendronate monosodium trihydrate Alendronate Sodium (200 mg) alendronate sodium hydrate Alendronate sodium trihydrate alendronate trihydrate Alendronic acid monosodium salt trihydrate Dronal Fosamsx G-704650 hydrogène (4-amino-1-hydroxy-1-phosphonobutyl)phosphonate de sodium trihydrate MFCD01748233 Monosodium (4-Amino-1-hydroxy-1-phosphonobutyl)phosphonate Trihydrate MonosodiuM Alendronate Trihydrate Natriumhydrogen-(4-amino-1-hydroxy-1-phosphonobutyl)phosphonattrihydrat onclast P,P'-(4-Amino-1-hydroxybutylidene)bis-phosphonicacidmonosodiumsalt Phosphonic acid, (4-amino-1-hydroxybutylidene)bis-, hydrate (1:3) Phosphonic acid, (4-amino-1-hydroxybutylidene)bis-, sodium salt, hydrate (1:1:3) Sodium alendronate Sodium Alendronate Trihydrate SodiuM Alendronate, EP Sodium hydrogen (4-amino-1-hydroxy-1-phosphonobutyl)phosphonate hydrate (1:1:3)

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1.3 CAS No.
121268-17-5
1.4 CID
23681107
1.5 EINECS(EC#)
601-766-4
1.6 Molecular Formula
C4H18NNaO10P2 (isomer)
1.7 Inchi
InChI=1S/C4H13NO7P2.Na.3H2O/c5-3-1-2-4(6,13(7,8)9)14(10,11)12;;;;/h6H,1-3,5H2,(H2,7,8,9)(H2,10,11,12);;3*1H2/q;+1;;;/p-1
1.8 InChIkey
DCSBSVSZJRSITC-UHFFFAOYSA-M
1.9 Canonical Smiles
C(CC(O)(P(=O)(O)O)P(=O)(O)[O-])CN.O.O.O.[Na+]
1.10 Isomers Smiles
C(CC(O)(P(=O)(O)O)P(=O)(O)[O-])CN.O.O.O.[Na+]
2. Properties
2.1 Density
1.857
2.1 Melting point
245℃
2.1 Boiling point
616.7 °C at 760 mmHg
2.1 Flash Point
326.7 °C
2.1 Precise Quality
325.03000
2.1 PSA
211.45000
2.1 logP
-0.32760
2.1 Solubility
water, double-distilled: 10?mg/mL
2.2 Appearance
White Crystalline Solid
2.3 Storage
?20°C
2.4 Chemical Properties
White Crystalline Solid
2.5 Color/Form
white
2.6 Water Solubility
water, double-distilled: 10 mg/mL soluble in water at 10mg/ml
2.7 Stability
Store in freezer
2.8 StorageTemp
-20°C
3. Use and Manufacturing
3.1 Definition
ChEBI: A hydride that is the trihydrate of alendronate sodium
3.2 GHS Classification
Signal: Danger
GHS Hazard Statements
Aggregated GHS information provided by 71 companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria by 2 of 71 companies. For more detailed information, please visit ECHA C&L website

Of the 9 notification(s) provided by 69 of 71 companies with hazard statement code(s):

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]
H315 (60.87%): Causes skin irritation [Warning Skin corrosion/irritation]
H318 (55.07%): Causes serious eye damage [Danger Serious eye damage/eye irritation]
H335 (62.32%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]
H361 (49.28%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]
H373 (50.72%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

Precautionary Statement Codes
P201, P202, P260, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P330, P332+P313, P362, P403+P233, P405, and P501
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3.3 Methods of Manufacturing
All chemicals were commercially purchased from Sigma Aldrich and used without further purification. Sodium carbonate, NaPreparation of alendronic acid monosodium salt; A mixture of 4-amino-butyric acid (10. Og, 0.097mol) and phosphorous acid (15.9g, 0.194mol) in acetonitrile (150ml) was heated at a temperature of 55-65°C and phosphorous trichloride (26.6g, 0.194mol) was added slowly under stirring. After completion of the addition, the reaction temperature was raised to 70-75Step 1: A mixture of 4-amino-butyric acid (10.0 g, 0.097 mol) and phosphorous acid (15.9 g, 0.194 mol) in acetonitrile (150 ml) was heated at a temperature of 55-65° C. and phosphorous trichloride (26.6 g, 0.194 mol) was added slowly under stirring. After completion of the addition, the reaction temperature was raised to 70-75° C. and the reaction continued for 6-9 hours at the same temperature. The reaction mixture was cooled to 60-65° C. and water (150 ml) was added slowly at the same temperature. The reaction temperature was then increased to 90-100° C. and maintained for the next 4-6 hours. The reaction mixture was then cooled to 55-65° C. and the reaction mixture pH was adjusted to 4.4-4.8 with sodium hydroxide solution. The reaction mixture was cooled to 25-35° C. and the aqueous layer containing the product was separated from the upper acetonitrile layer. The aqueous layer was cooled to and maintained at 0-5° C. for 3 hours. The solid product was separated by filtration and washed with water and finally with methanol to obtain sodium alendronate. The product was dried in a vacuum oven at 45-50° C. until loss on drying was less than 0.5percent w/w. Yield: 16 g (69.6percent). Appearance: almost white powder. Melting range: 234-238° C. (with decomposition).2.6 g (0.025 mol) of -γaminobutyric acid and 6.2 g (0.075mol) of phosphorous acid was added into 6.8 mL of MSA on stirring. Then 7.0 mL (0.075 mol) of phosphoryl chloride was added dropwise in ca. 15 min, and the contents of the flask were stirred at 75°C for 12 h. After cooling the mixture to 26°C, 19 mL (1.1 mol) of water was added and the mixture was stirred further at 105°C for 4 h. The pH was adjusted to 1.8 by adding ~12 mL of 50percent aqueous sodium hydroxide to the mixture. Then, the mixture was stirred at room temperature for 2 h and the precipitate was removed by filtration. The crude product was suspended in 50 mL ofwater and the mixture was stirred at 100°C for 1 h, then the pH was adjusted to 4, 5. After cooling the mixture to 26°C, the solid product was filtered off to give 5.0 g (60percent) of sodium alendronate trihydrate (8) in a purity of 97percent.3.8 mmol (1 equiv) of the respective carboxylic acid (658 mg 3-pyridylacetic acid hydrochloride for 1, 478 mg imidazol-1-yl-acetic acid for 2, 339 mg β-alanine for 3, 392 mg γ-aminobutyric acid for 4, 499 mg 6-aminohexanoic acid for 5) were added to 11.4 mmol (3 equiv) HTo a 250 ml reaction vessel equipped with a water condenser, 8.5 gm (0.1 mol) pyrrolidone, and 33.5 ml water was added under nitrogen atmosphere. Then, 17.2 gm (0.125 mol) PCl To a 250 ml reaction vessel equipped with water condenser, 8.5 gm (0.1 mol) pyrrolidone, and 33.5 ml water was added under nitrogen atmosphere. Then 17.2 gm (0.125 mol) PCl In a 250 reaction vessel equipped with water condenser, 8.5 gm (0.1 mol) pyrrolidone, 14 ml water and 11.5 gm methane sulphonic acid was added under nitrogen atmosphere. At room temperature 17.2 gm (11 ml, 0.125 mol) PClIn a 250 reaction vessel equipped with a water condenser, 8.5 gm (0.1 mol) pyrrolidone, 14 ml water, and 11.5 gm methane sulphonic acid were added under a nitrogen atmosphere. At room temperature, 17.2 gm (11 ml, 0.125 mol) PClExample 3 In a reaction vessel, 17.0 g(0.2 mol) pyrrolidone, 22 ml water and 23 gm methane sulphonic acid were taken and was heated to reflux (105 °C) for 9 hours or till the disappearance of pyrrolidone (monitored by TLC method). The mass was cooled to room temperature and PCl3 (17.5 ml, 0.199 mol) was added drop-wise while maintaining the temperature below 65 °C. Further the reaction was stirred at 60-65 °C for 30 minutes and then the temperature was raised to 110 °C, water was continuously distilled under vacuum. The mass was then cooled to 60 °C and added a further quantity of 90.39 gm (57.5 ml, 0.6565 mol) PCl3 was added drop-wise while maintaining the temperature below 60 °C followed by 25.5 ml of HEXAMPLE 3 In a reaction vessel, 17.0 g (0.2 mol) pyrrolidone, 22 ml water, and 23 gm methane sulphonic acid were mixed and then heated to reflux (i.e., 105° C.) for 9 hours or till the disappearance of pyrrolidone was observed (monitored by TLC method). The mass was then cooled to room temperature and PCl
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3.4 Usage
A bisphosphonate used as a bone reabsoption inhibitor
4. Safety and Handling
4.1 Symbol
GHS07
4.1 Hazard Codes
Xn; Xi
4.1 Signal Word
Warning
4.1 Risk Statements
22-36/37/38
4.1 Safety Statements
26-36-60
4.1 Hazard Declaration
H302
4.1 RIDADR
NONH for all modes of transport
4.1 Caution Statement
P301 + P312 + P330
4.1 WGK Germany
3
4.1 RTECS
SZ6523500
4.1 Safety

A poison by intravenous route. Experimental reproductive effects. When heated to decomposition it emits toxic vapors of NOx, POx, and NaO.
Hazard Codes:?HarmfulXn,IrritantXi
The Risk Statements:
22:? Harmful if swallowed?
36/37/38:? Irritating to eyes, respiratory system and skin
The Safety Statements:
26:? In case of contact with eyes, rinse immediately with plenty of water and seek medical advice?
36:? Wear suitable protective clothing??
WGK Germany: 3

4.2 Specification

?Alendronate sodium , its cas register number is 121268-17-5. It also can be called Fosamax ; Monosodium alendronate ; Alendronic acid monosodium salt ; Fosalan ; Alendros ; Bifosa ; NeoBon ; 4-Amino-1-hydroxybutylidene-1,1-bisphosphonic acid monosodium salt ; and Osteovan .?It is marketed alone as well as in combination with vitamin D, and Merck's U.S. patent on alendronate expired in 2008 and Merck lost a series of appeals to block a generic version of the drug from being certified by the U.S. Food and Drug Administration (FDA).?Alendronate inhibits osteoclast-mediated bone-resorption.

4.3 Toxicity
1. ???

ivn-rat LDLo:30?mg/kg

??? KSRNAM ?? Kiso to Rinsho. Clinical Report. 28 (1994),3229.
2. ???

ivn-dog LDLo:10?mg/kg

??? KSRNAM ?? Kiso to Rinsho. Clinical Report. 28 (1994),3229.
5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Skin irritation, Category 2

Serious eye damage, Category 1

Specific target organ toxicity \u2013 single exposure, Category 3

Reproductive toxicity, Category 2

Specific target organ toxicity \u2013 repeated exposure, Category 2

Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 3

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word

Danger

Hazard statement(s)

H302 Harmful if swallowed

H315 Causes skin irritation

H318 Causes serious eye damage

H335 May cause respiratory irritation

H361 Suspected of damaging fertility or the unborn child

H373 May cause damage to organs through prolonged or repeated exposure

H412 Harmful to aquatic life with long lasting effects

Precautionary statement(s)
Prevention

P264 Wash ... thoroughly after handling.

P270 Do not eat, drink or smoke when using this product.

P280 Wear protective gloves/protective clothing/eye protection/face protection.

P261 Avoid breathing dust/fume/gas/mist/vapours/spray.

P271 Use only outdoors or in a well-ventilated area.

P201 Obtain special instructions before use.

P202 Do not handle until all safety precautions have been read and understood.

P260 Do not breathe dust/fume/gas/mist/vapours/spray.

P273 Avoid release to the environment.

Response

P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell.

P330 Rinse mouth.

P302+P352 IF ON SKIN: Wash with plenty of water/...

P321 Specific treatment (see ... on this label).

P332+P313 If skin irritation occurs: Get medical advice/attention.

P362+P364 Take off contaminated clothing and wash it before reuse.

P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.

P310 Immediately call a POISON CENTER/doctor/\u2026

P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing.

P312 Call a POISON CENTER/doctor/\u2026if you feel unwell.

P308+P313 IF exposed or concerned: Get medical advice/ attention.

P314 Get medical advice/attention if you feel unwell.

Storage

P403+P233 Store in a well-ventilated place. Keep container tightly closed.

P405 Store locked up.

Disposal

P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

7. Precursor and Product
8. Other Information
8.0 Merck
14,229
8.1 Chemical Properties
White Crystalline Solid
8.2 Uses
A bisphosphonate used as a bone reabsoption inhibitor
8.3 Uses
dopamine receptor agonist, antiParkinsonian
8.4 Uses
Inhibits bone resorption and increases bone density.
8.5 Definition
ChEBI: A hydride that is the trihydrate of alendronate sodium
8.6 Brand name
Fosamax (Merck).
8.7 Originator
Adronat ,Neopharmed ,Italy
8.8 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-flask with condenser, stirrer and dropping funnel, placed on a thermostatized bath; the air is then removed with a nitrogen stream which is continued during all the reaction. The acid is melted by heating the bath to 95°C. When melting is complete, 4-aminobutyric acid (103.3; 1 mole) is added under stirring which is continued till obtaining a doughy fluid. Phosphorous trihalide (176 ml; 2 moles) is added dropwise causing the mixture to boil and evolution of gaseous hydrochloric acid which is damped by means of a suitable trap. The addition rate is adjusted so as to keep a constant reflux for about 60 minutes. When the addition is nearly over, the mixture swells, slowly hardening. Stirring is continued as long as possible, whereafter the mixture is heated for further 3 hours. Without cooling, but removing the bath, water (300 ml) is added, first slowly and then quickly. Heating and stirring are started again. Decolorizing charcoal is added and the mixture is boiled for about 5 minutes, then hotfiltered on paper and the filtrate is refluxed for 6 hours. After cooling is slowly poured in stirred methanol (1500 ml) causing thereby the separation of a white solid which collected and dried (161 g; 64.6%). The structure of ABDT is confirmed by IR spectrum, proton magnetic and nuclear magnetic resonance spectrum and elemental analysis.
The sodium salt of this acid may be prepared by adding of equivalent of sodium hydroxide.
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8.9 Therapeutic Function
Antiosteoporotic
8.10 General Description
Alendronate Sodium, an aminobisphosphonate compound, has been effectively used for the treatment of osteolysis, Paget′s disease and osteoporosis.
8.11 Storage Conditions
All chemicals were commercially purchased from Sigma Aldrich and used without further purification. Sodium carbonate, NaPreparation of alendronic acid monosodium salt; A mixture of 4-amino-butyric acid (10. Og, 0.097mol) and phosphorous acid (15.9g, 0.194mol) in acetonitrile (150ml) was heated at a temperature of 55-65°C and phosphorous trichloride (26.6g, 0.194mol) was added slowly under stirring. After completion of the addition, the reaction temperature was raised to 70-75Step 1: A mixture of 4-amino-butyric acid (10.0 g, 0.097 mol) and phosphorous acid (15.9 g, 0.194 mol) in acetonitrile (150 ml) was heated at a temperature of 55-65° C. and phosphorous trichloride (26.6 g, 0.194 mol) was added slowly under stirring. After completion of the addition, the reaction temperature was raised to 70-75° C. and the reaction continued for 6-9 hours at the same temperature. The reaction mixture was cooled to 60-65° C. and water (150 ml) was added slowly at the same temperature. The reaction temperature was then increased to 90-100° C. and maintained for the next 4-6 hours. The reaction mixture was then cooled to 55-65° C. and the reaction mixture pH was adjusted to 4.4-4.8 with sodium hydroxide solution. The reaction mixture was cooled to 25-35° C. and the aqueous layer containing the product was separated from the upper acetonitrile layer. The aqueous layer was cooled to and maintained at 0-5° C. for 3 hours. The solid product was separated by filtration and washed with water and finally with methanol to obtain sodium alendronate. The product was dried in a vacuum oven at 45-50° C. until loss on drying was less than 0.5percent w/w. Yield: 16 g (69.6percent). Appearance: almost white powder. Melting range: 234-238° C. (with decomposition).2.6 g (0.025 mol) of -γaminobutyric acid and 6.2 g (0.075mol) of phosphorous acid was added into 6.8 mL of MSA on stirring. Then 7.0 mL (0.075 mol) of phosphoryl chloride was added dropwise in ca. 15 min, and the contents of the flask were stirred at 75°C for 12 h. After cooling the mixture to 26°C, 19 mL (1.1 mol) of water was added and the mixture was stirred further at 105°C for 4 h. The pH was adjusted to 1.8 by adding ~12 mL of 50percent aqueous sodium hydroxide to the mixture. Then, the mixture was stirred at room temperature for 2 h and the precipitate was removed by filtration. The crude product was suspended in 50 mL ofwater and the mixture was stirred at 100°C for 1 h, then the pH was adjusted to 4, 5. After cooling the mixture to 26°C, the solid product was filtered off to give 5.0 g (60percent) of sodium alendronate trihydrate (8) in a purity of 97percent.3.8 mmol (1 equiv) of the respective carboxylic acid (658 mg 3-pyridylacetic acid hydrochloride for 1, 478 mg imidazol-1-yl-acetic acid for 2, 339 mg β-alanine for 3, 392 mg γ-aminobutyric acid for 4, 499 mg 6-aminohexanoic acid for 5) were added to 11.4 mmol (3 equiv) HTo a 250 ml reaction vessel equipped with a water condenser, 8.5 gm (0.1 mol) pyrrolidone, and 33.5 ml water was added under nitrogen atmosphere. Then, 17.2 gm (0.125 mol) PCl To a 250 ml reaction vessel equipped with water condenser, 8.5 gm (0.1 mol) pyrrolidone, and 33.5 ml water was added under nitrogen atmosphere. Then 17.2 gm (0.125 mol) PCl In a 250 reaction vessel equipped with water condenser, 8.5 gm (0.1 mol) pyrrolidone, 14 ml water and 11.5 gm methane sulphonic acid was added under nitrogen atmosphere. At room temperature 17.2 gm (11 ml, 0.125 mol) PClIn a 250 reaction vessel equipped with a water condenser, 8.5 gm (0.1 mol) pyrrolidone, 14 ml water, and 11.5 gm methane sulphonic acid were added under a nitrogen atmosphere. At room temperature, 17.2 gm (11 ml, 0.125 mol) PClExample 3 In a reaction vessel, 17.0 g(0.2 mol) pyrrolidone, 22 ml water and 23 gm methane sulphonic acid were taken and was heated to reflux (105 °C) for 9 hours or till the disappearance of pyrrolidone (monitored by TLC method). The mass was cooled to room temperature and PCl3 (17.5 ml, 0.199 mol) was added drop-wise while maintaining the temperature below 65 °C. Further the reaction was stirred at 60-65 °C for 30 minutes and then the temperature was raised to 110 °C, water was continuously distilled under vacuum. The mass was then cooled to 60 °C and added a further quantity of 90.39 gm (57.5 ml, 0.6565 mol) PCl3 was added drop-wise while maintaining the temperature below 60 °C followed by 25.5 ml of HEXAMPLE 3 In a reaction vessel, 17.0 g (0.2 mol) pyrrolidone, 22 ml water, and 23 gm methane sulphonic acid were mixed and then heated to reflux (i.e., 105° C.) for 9 hours or till the disappearance of pyrrolidone was observed (monitored by TLC method). The mass was then cooled to room temperature and PCl
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8.12 Usage
Alendronate sodium trihydrate is used as a bone resorption inhibitor, farnesyl diphosphate synthase inhibitor and CD45 protein tyrosine phosphatase inhibitor. A robust inhibitor of bone resorption that induces apoptosis. Alendronate inhibits the migration and invasion of PC-3 cells (sc-2220) by interfering with the mevalonate pathway. Additionally, Alendronate, Sodium Salt is an inhibitor of CD45RC and MMP.
9. Computational chemical data
  • Molecular Weight: 325.122g/mol
  • Molecular Formula: C4H18NNaO10P2
  • Compound Is Canonicalized: True
  • XLogP3-AA: null
  • Exact Mass: 325.03036405
  • Monoisotopic Mass: 325.03036405
  • Complexity: 293
  • Rotatable Bond Count: 5
  • Hydrogen Bond Donor Count: 8
  • Hydrogen Bond Acceptor Count: 11
  • Topological Polar Surface Area: 167
  • Heavy Atom Count: 18
  • Defined Atom Stereocenter Count: 0
  • Undefined Atom Stereocenter Count: 1
  • Defined Bond Stereocenter Count: 0
  • Undefined Bond Stereocenter Count: 0
  • Isotope Atom Count: 0
  • Covalently-Bonded Unit Count: 5
  • CACTVS Substructure Key Fingerprint: AAADceBiPCMAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAHggQCCAACADBgAQAAABAAhAAQAAAAIAAAAAAAAAAAIAAAAAAAAAAgAAAQAAEEAAAAAAgAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==
10. Question & Answer
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12. Realated Product Infomation