(4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid

• ChemBase ID: 512
• Molecular Formular: C4H13NO7P2
• Molecular Mass: 249.096042
• Monoisotopic Mass: 249.01672502
• SMILES: P(=O)(O)(O)C(P(=O)(O)O)(O)CCCN
• Canonical SMILES: NCCCC(P(=O)(O)O)(P(=O)(O)O)O
• InChI: InChI=1S/C4H13NO7P2/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)
• InChIKey: OGSPWJRAVKPPFI-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid
• IUPAC Traditional name: alendronate
• Brand Name: Adronat; Alendros; Arendal; Fosamax; Onclast; Fosamax Plus D
• Synonyms: Acide Alendronique [INN-French]; Acido Alendronico [INN-Spanish]; Acidum Alendronicum [INN-Latin]; Alendronate Sodium; Alendronic acid; Alendronate; ALENDRONATE SODIUM

Database IDs

• CAS Number: 66376-36-1; 121268-17-5
• PubChem SID: 160963975; 46507199
• PubChem CID: 2088

CALCULATED PROPERTIES

JChem

• Acid pKa: 0.69048136
• H Acceptors: 8
• H Donor: 6
• LogD (pH = 5.5): -6.231197
• LogD (pH = 7.4): -6.5565596
• Log P: -4.190998
• Molar Refractivity: 47.3738 cm^3
• Polarizability: 19.192327 Å^3
• Polar Surface Area: 161.31 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: -1.34
• LOG S: -1.17
• Solubility (Water): 1.69e+01 g/l

PROPERTIES

Physical Property

• Solubility: 1mg/L
• Hydrophobicity(logP): -4.3

Product Information

• Purity: 98%

DETAILS

DrugBank - DB00630

• Drug Groups: approved
• Description: Alendronate is a nitrogen-containing, second generation bisphosphonate. Bisphosphonates were first used to treat Paget’s disease in 1971. This class of medications is comprised of inorganic pyrophosphate analogues that contain non-hydrolyzable P-C-P bonds. Similar to other bisphosphonates, alendronate has a high affinity for bone mineral and is taken up during osteoclast resorption. Alendronate inhibits farnesyl pyrophosphate synthetase, one of the enzymes in the mevalonic acid pathway involved in producing isoprenoid compounds that are essential for post-translational modification of small guanosine triphosphate (GTP)-binding proteins, such as Rho, Ras and Rab. Inhibition of this process interferes with osteoclast function and survival. Alendronate is used for the treatment of osteoporosis and Paget’s disease.
• Indication: For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women.
• Pharmacology: Alendronate, a second-generation bisphosphonate is the first member of a group of drugs which strengthens bone. Alendronate is used to reduce hypercalcemia in tumor-induced bone disease, to treat corticosteroid-induced osteoporosis and Paget's disease, and to prevent osteoporosis in postmenopausal women.
• Toxicity: Alendronate can damage the esophagus both by toxicity from the medication itself and by nonspecific irritation secondary to contact between the pill and the esophageal mucosa, similar to other cases of "pill esophagitis."
• Affected Organisms: Humans and other mammals
• Biotransformation: There is no evidence that alendronate is metabolized in humans or animals.
• Absorption: Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast.
• Half Life: >10 years
• Protein Binding: 78%
• Elimination: Following a single IV 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 feces.
• Distribution: * 28 L
• Clearance: * <200 mL/min [A single 10?mg IV dose]
• References: Russell RG, Watts NB, Ebetino FH, Rogers MJ: Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun;19(6):733-59. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Russell RG, Watts NB, Ebetino FH, Rogers MJ: Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun;19(6):733-59. Pubmed