ethyl (3R,4R,5S)-5-amino-4-acetamido-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate

• ChemBase ID: 83
• Molecular Formular: C16H28N2O4
• Molecular Mass: 312.40452
• Monoisotopic Mass: 312.20490739
• SMILES: O([C@H]1[C@H](NC(=O)C)[C@@H](N)CC(=C1)C(=O)OCC)C(CC)CC
• Canonical SMILES: CCOC(=O)C1=C[C@H]([C@@H]([C@H](C1)N)NC(=O)C)OC(CC)CC
• InChI: InChI=1S/C16H28N2O4/c1-5-12(6-2)22-14-9-11(16(20)21-7-3)8-13(17)15(14)18-10(4)19/h9,12-15H,5-8,17H2,1-4H3,(H,18,19)/t13-,14+,15+/m0/s1
• InChIKey: VSZGPKBBMSAYNT-RRFJBIMHSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: ethyl (3R,4R,5S)-5-amino-4-acetamido-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate
• IUPAC Traditional name: oseltamivir
• Brand Name: Tamiflu
• Synonyms: Oseltamivir phosphate; Oseltamivir

Database IDs

• CAS Number: 204255-11-8
• PubChem SID: 160963546; 46507602
• PubChem CID: 65028

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.033634
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): -1.8032612
• LogD (pH = 7.4): -0.7199175
• Log P: 1.1625985
• Molar Refractivity: 84.2034 cm^3
• Polarizability: 33.440342 Å^3
• Polar Surface Area: 90.65 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.3
• LOG S: -2.66
• Solubility (Water): 6.86e-01 g/l

PROPERTIES

Physical Property

• Solubility: Soluble
• Hydrophobicity(logP): 1

DETAILS

DrugBank - DB00198

• Drug Groups: approved
• Description: An acetamido cyclohexene that is a structural homolog of sialic acid and inhibits neuraminidase. [PubChem]
• Indication: Oseltamivir (Tamiflu) is for the treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older who have been symptomatic for no more than 2 days. It is also used for the prophylaxis of influenza in adult patients and adolescents 13 years and older.
• Pharmacology: Oseltamivir is an antiviral drug, a neuraminidase inhibitor used in the treatment and prophylaxis of both influenza A and influenza B. Oseltamivir is a prodrug (usually administered as phosphate), it is hydrolysed hepatically to the active metabolite, the free carboxylate of oseltamivir (GS4071). Like zanamivir, oseltamivir acts as a transition-state analogue inhibitor of influenza neuraminidase.
• Toxicity: At present, there has been no experience with overdose. Single doses of up to 1000 mg of oseltamivir have been associated with nausea and/or vomiting. Mean LD (intravenous, mouse) = 100 mg/kg.
• Affected Organisms: Influenza Virus
• Biotransformation: Extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms. At least 75% of an oral dose reaches the systemic circulation as oseltamivir carboxylate.
• Absorption: Readily absorbed from the gastrointestinal tract after oral administration with a bioavailability of 75%.
• Half Life: 1 to 3 hours in most subjects after oral administration.
• Protein Binding: Oseltamivir carboxylate: low (3%), Oseltamivir free base: 42%.
• Elimination: Absorbed oseltamivir is primarily (>90%) eliminated by conversion to oseltamivir carboxylate. Oseltamivir carboxylate is not further metabolized and is eliminated in the urine. Oseltamivir carboxylate is eliminated entirely (>99%) by renal excretion.
• Distribution: * 23 to 26 L
• References: Chokephaibulkit K, Uiprasertkul M, Puthavathana P, Chearskul P, Auewarakul P, Dowell SF, Vanprapar N: A child with avian influenza A (H5N1) infection. Pediatr Infect Dis J. 2005 Feb;24(2):162-6. [Pubmed] ; de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J: Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005 Dec 22;353(25):2667-72. [Pubmed] ; Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y: Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004 Aug 28-Sep 3;364(9436):759-65. [Pubmed] ; Ward P, Small I, Smith J, Suter P, Dutkowski R: Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005 Feb;55 Suppl 1:i5-i21. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Chokephaibulkit K, Uiprasertkul M, Puthavathana P, Chearskul P, Auewarakul P, Dowell SF, Vanprapar N: A child with avian influenza A (H5N1) infection. Pediatr Infect Dis J. 2005 Feb;24(2):162-6. Pubmed
• de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J: Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005 Dec 22;353(25):2667-72. Pubmed
• Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y: Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004 Aug 28-Sep 3;364(9436):759-65. Pubmed
• Ward P, Small I, Smith J, Suter P, Dutkowski R: Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005 Feb;55 Suppl 1:i5-i21. Pubmed