({2-[(3-aminopropyl)amino]ethyl}sulfanyl)phosphonic acid

• ChemBase ID: 1014
• Molecular Formular: C5H15N2O3PS
• Molecular Mass: 214.222961
• Monoisotopic Mass: 214.05409998
• SMILES: S(P(=O)(O)O)CCNCCCN
• Canonical SMILES: NCCCNCCSP(=O)(O)O
• InChI: InChI=1S/C5H15N2O3PS/c6-2-1-3-7-4-5-12-11(8,9)10/h7H,1-6H2,(H2,8,9,10)
• InChIKey: JKOQGQFVAUAYPM-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: ({2-[(3-aminopropyl)amino]ethyl}sulfanyl)phosphonic acid
• IUPAC Traditional name: amifostine
• Brand Name: Ethyol
• Synonyms: Aminopropylaminoethyl Thiophosphate; WR-1065; Apaetp; SAPEP; Amifostine Ethiofos; Ethiofos; Gammaphos; amifostine; Amifostine; 2-(3-Aminopropyl)aminoethyl phosphorothioate; WR2721; Amifostine; 2-[(3-Aminopropyl)-amino]ethanethiol Dihydrogen Phosphate; Phosphorothioic Acid S-[2-[(3-Aminopropyl)amino]ethyl]ester; CSC-296961; Ethyol

Database IDs

• CAS Number: 20537-88-6
• MDL Number: MFCD00233058
• PubChem SID: 46505305; 160964477; 24278231
• PubChem CID: 2141

CALCULATED PROPERTIES

JChem

• Acid pKa: 2.0575242
• H Acceptors: 5
• H Donor: 4
• LogD (pH = 5.5): -4.9497204
• LogD (pH = 7.4): -3.7830431
• Log P: -3.7403424
• Molar Refractivity: 51.2831 cm^3
• Polarizability: 20.384901 Å^3
• Polar Surface Area: 95.58 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -1.44
• LOG S: -1.06
• Solubility (Water): 1.87e+01 g/l

PROPERTIES

Physical Property

• Solubility: 1000 mg/mL; Water
• Apperance: powder; White Solid
• Melting Point: 144-148°C
• Hydrophobicity(logP): -1.9

Safety Information

• Storage Condition: Refrigerator
• RTECS: TE6491000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22
• Safety Statements: 26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: 2-8°C

Product Information

• Purity: ≥97% (TLC)
• Empirical Formula (Hill Notation): C5H15N2O3PS

DETAILS

DrugBank - DB01143

• Drug Groups: approved; investigational
• Description: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [PubChem]
• Indication: For reduction in the cumulative renal toxicity in patients with ovarian cancer (using cisplatin) and moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer.
• Pharmacology: Amifostine is an organic thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or non-small cell lung cancer and also to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer. Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite, believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumour cells.
• Toxicity: Rat LD₅₀: 826 mg/kg
• Affected Organisms: Humans and other mammals
• Biotransformation: Amifostine is rapidly dephosphorylated by alkaline phosphatase in tissues primarily to the active free thiol metabolite and, subsequently, to a less active disulfide metabolite.
• Half Life: 8 minutes
• Elimination: After a 10-second bolus dose of 150 mg/m2 of ETHYOL, renal excretion of the parent drug and its two metabolites was low during the hour following drug administration, averaging 0.69%, 2.64% and 2.22% of the administered dose for the parent, thiol and disulfide, respectively.
• References: Santini V, Giles FJ: The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035-42. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - A5922

Application
Amifostine may provide renal protection during PRRT using somatostatin analogs by mitigating radiation damage and reducing the absorbed kidney radiation dose. Amifostine remediates the degenerative effects of radiation on the mineralization capacity of the murine mandible.
Biochem/physiol Actions
Radioprotective agent. Selectively protects normal tissues from the damaging effects of anti-neoplastic radiation therapy. Selectivity is due to preferential uptake by normal tissues and subsequent metabolic activation to 2-(3-aminopropyl)aminoethanethiol.

Toronto Research Chemicals - A576810

It is a thiophosphate derivative of cysteamine; provides normal cells with selective protection against the toxic effects of cancer chemotherapy and radiation treatment.

REFERENCES

• Santini V, Giles FJ: The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035-42. Pubmed
• Brown, D.Q., et al. Pharmacol. Ther., 39, 159 (1988)
• Capizzi, R.L., et al.: Cancer, 72, 3495 (1988)
• Treskes, M., et al.: Cancer Chemother. Pharmacol., 33, 93 (1988)