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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2018-05-20 20:48:14 UTC
HMDB IDHMDB0014343
Secondary Accession Numbers
  • HMDB14343
Metabolite Identification
Common NameOseltamivir
DescriptionOseltamivir is only found in individuals that have used or taken this drug. It is an acetamido cyclohexene that is a structural homolog of sialic acid and inhibits neuraminidase. [PubChem]Oseltamivir is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. The proposed mechanism of action of oseltamivir is inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release.
Structure
Thumb
Synonyms
ValueSource
(-)-OseltamivirChEBI
AgucortChEBI
Ethyl (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylateChEBI
GS-4104ChEBI
HSDB 7433ChEBI
OseltamivirumChEBI
TamifluChEBI
Ethyl (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acidGenerator
Oseltamivir phosphateHMDB
Chemical FormulaC16H28N2O4
Average Molecular Weight312.4045
Monoisotopic Molecular Weight312.204907394
IUPAC Nameethyl (3R,4R,5S)-5-amino-4-acetamido-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate
Traditional Nameoseltamivir
CAS Registry Number204255-11-8
SMILES
CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1
InChI Identifier
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
InChI KeyVSZGPKBBMSAYNT-RRFJBIMHSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGamma amino acids and derivatives
Alternative Parents
Substituents
  • Gamma amino acid or derivatives
  • Enoate ester
  • Acetamide
  • Alpha,beta-unsaturated carboxylic ester
  • Carboxamide group
  • Carboxylic acid ester
  • Secondary carboxylic acid amide
  • Dialkyl ether
  • Ether
  • Monocarboxylic acid or derivatives
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Primary aliphatic amine
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Primary amine
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.69 g/LNot Available
LogP1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.69 g/LALOGPS
logP1.3ALOGPS
logP1.16ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)14.03ChemAxon
pKa (Strongest Basic)9.31ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area90.65 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity84.2 m³·mol⁻¹ChemAxon
Polarizability34.65 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05bo-9280000000-03554fbfb24a606e4a9aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-01t9-0193000000-f5d60d35ef59bb0d3d88View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0930000000-4bafe71e1cfce532c69eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0900000000-b47b81a2da926f1b38a0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-01bi-0900000000-e54a66b05b36ac125c76View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00dr-0900000000-a088a5ae7a49e423f645View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-a4689c9d2708c9864683View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-07fr-0393000000-c4ca6313b8a95857501fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-014i-0920000000-274bd00e87c126ea0431View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-014i-1900000000-ab2b530339386266bb5eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00y3-3900000000-503de5f1484e1733b933View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-006x-6900000000-c732121f239f135b134cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-006x-9600000000-414288f436e77a96401fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-07fr-0393000000-782bc585f56c5193cc4eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-014i-0920000000-2a6c0c1f08190d6bbc0fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-014i-1900000000-3ea178c0a288c37e3e79View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00y3-3900000000-0c790adae380f41f557aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-006x-6900000000-793d9a5e1ce9de381e4fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-006x-9600000000-ebf8dd7bcfb3a4844078View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-f5e9b54d2909b3aff88dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-044j-1092000000-a5c51c03276e29381b54View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0gi0-1290000000-855d80ff3dbaf863b55bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9720000000-3020e017c27cf5688ae5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-2089000000-aca6af58f0479c615bbcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02t9-2091000000-dafdec8458549b80e2b6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ap1-9830000000-e6541c125795bb30888fView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00198 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00198 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00198
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID58540
KEGG Compound IDC08092
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkOseltamivir
METLIN IDNot Available
PubChem Compound65028
PDB IDNot Available
ChEBI ID7798
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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:15337401 ]
  2. 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:15702046 ]
  3. 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:15709056 ]
  4. 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:16371632 ]

Enzymes

General function:
Involved in exo-alpha-sialidase activity
Specific function:
Hydrolyzes sialylated compounds.
Gene Name:
NEU2
Uniprot ID:
Q9Y3R4
Molecular weight:
Not Available
References
  1. Chavas LM, Kato R, Suzuki N, von Itzstein M, Mann MC, Thomson RJ, Dyason JC, McKimm-Breschkin J, Fusi P, Tringali C, Venerando B, Tettamanti G, Monti E, Wakatsuki S: Complexity in influenza virus targeted drug design: interaction with human sialidases. J Med Chem. 2010 Apr 8;53(7):2998-3002. doi: 10.1021/jm100078r. [PubMed:20222714 ]
General function:
Involved in exo-alpha-sialidase activity
Specific function:
Catalyzes the removal of sialic acid (N-acetylneuramic acid) moities from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.
Gene Name:
NEU1
Uniprot ID:
Q99519
Molecular weight:
Not Available
References
  1. Chavas LM, Kato R, Suzuki N, von Itzstein M, Mann MC, Thomson RJ, Dyason JC, McKimm-Breschkin J, Fusi P, Tringali C, Venerando B, Tettamanti G, Monti E, Wakatsuki S: Complexity in influenza virus targeted drug design: interaction with human sialidases. J Med Chem. 2010 Apr 8;53(7):2998-3002. doi: 10.1021/jm100078r. [PubMed:20222714 ]
General function:
Lipid transport and metabolism
Specific function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.
Gene Name:
CES1
Uniprot ID:
P23141
Molecular weight:
62520.62
References
  1. Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B: Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther. 2006 Dec;319(3):1477-84. Epub 2006 Sep 11. [PubMed:16966469 ]
  2. Wattanagoon Y, Stepniewska K, Lindegardh N, Pukrittayakamee S, Silachamroon U, Piyaphanee W, Singtoroj T, Hanpithakpong W, Davies G, Tarning J, Pongtavornpinyo W, Fukuda C, Singhasivanon P, Day NP, White NJ: Pharmacokinetics of high-dose oseltamivir in healthy volunteers. Antimicrob Agents Chemother. 2009 Mar;53(3):945-52. doi: 10.1128/AAC.00588-08. Epub 2008 Dec 22. [PubMed:19104028 ]
  3. Zhu HJ, Markowitz JS: Activation of the antiviral prodrug oseltamivir is impaired by two newly identified carboxylesterase 1 variants. Drug Metab Dispos. 2009 Feb;37(2):264-7. doi: 10.1124/dmd.108.024943. Epub 2008 Nov 20. [PubMed:19022936 ]

Transporters

General function:
Involved in transporter activity
Specific function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products
Gene Name:
SLC15A1
Uniprot ID:
P46059
Molecular weight:
78805.3
References
  1. Ogihara T, Kano T, Wagatsuma T, Wada S, Yabuuchi H, Enomoto S, Morimoto K, Shirasaka Y, Kobayashi S, Tamai I: Oseltamivir (tamiflu) is a substrate of peptide transporter 1. Drug Metab Dispos. 2009 Aug;37(8):1676-81. doi: 10.1124/dmd.109.026922. Epub 2009 May 13. [PubMed:19439487 ]
General function:
Involved in ATP binding
Specific function:
May be an organic anion pump relevant to cellular detoxification
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular weight:
149525.3
References
  1. Ose A, Ito M, Kusuhara H, Yamatsugu K, Kanai M, Shibasaki M, Hosokawa M, Schuetz JD, Sugiyama Y: Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21. doi: 10.1124/dmd.108.024018. Epub 2008 Nov 24. [PubMed:19029202 ]