(2R,3R,4S)-4-[(diaminomethylidene)amino]-3-acetamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid

• ChemBase ID: 440
• Molecular Formular: C12H20N4O7
• Molecular Mass: 332.3098
• Monoisotopic Mass: 332.133199
• SMILES: O1[C@H]([C@H](NC(=O)C)[C@@H](N=C(N)N)C=C1C(=O)O)[C@H](O)[C@H](O)CO
• Canonical SMILES: OC[C@H]([C@H]([C@@H]1OC(=C[C@@H]([C@H]1NC(=O)C)N=C(N)N)C(=O)O)O)O
• InChI: InChI=1S/C12H20N4O7/c1-4(18)15-8-5(16-12(13)14)2-7(11(21)22)23-10(8)9(20)6(19)3-17/h2,5-6,8-10,17,19-20H,3H2,1H3,(H,15,18)(H,21,22)(H4,13,14,16)/t5-,6+,8+,9+,10+/m0/s1
• InChIKey: ARAIBEBZBOPLMB-UFGQHTETSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R,3R,4S)-4-[(diaminomethylidene)amino]-3-acetamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
• IUPAC Traditional name: zanamivir
• Brand Name: Relenza
• Synonyms: ZMR; Modified sialic acid; GANA; GNA; Zanamavir; Zanamivir

Database IDs

• CAS Number: 139110-80-8
• PubChem SID: 46508581; 160963903
• PubChem CID: 60855

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.2536163
• H Acceptors: 10
• H Donor: 7
• LogD (pH = 5.5): -5.8297024
• LogD (pH = 7.4): -5.827702
• Log P: -5.8277187
• Molar Refractivity: 76.19 cm^3
• Polarizability: 29.490557 Å^3
• Polar Surface Area: 200.72 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: -2.3
• LOG S: -1.66
• Solubility (Water): 7.31e+00 g/l

PROPERTIES

Physical Property

• Solubility: 7.31 mg/mL [Predicted by ALOGPS]
• Hydrophobicity(logP): -3

DETAILS

DrugBank - DB00558

• Drug Groups: approved; investigational
• Description: A guanido-neuraminic acid that is used to inhibit neuraminidase. [PubChem]
• Indication: For the prevention and treatment of influenza A and B.
• Pharmacology: Zanamivir, an antiviral agent, is a neuraminidase inhibitor indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Zanamivir has also been shown to significantly inhibit the human sialidases NEU3 and NEU2 in the micromolar range (Ki 3.7 +/-0.48 and 12.9+/-0.07 microM, respectively), which could account for some of the rare side effects of zanamivir.
• Affected Organisms: Influenza A virus; Influenza B virus
• Biotransformation: Not metabolized
• Absorption: Absolute bioavailability is very low following oral administration (2%). Following oral inhalation, bioavailability is 4% to 17%.
• Half Life: 2.5-5.1 hours
• Protein Binding: Zanamivir has limited plasma protein binding (<10%).
• Elimination: It is excreted unchanged in the urine with excretion of a single dose completed within 24 hours.; Unabsorbed drug is excreted in the feces.Zanamivir is renally excreted as unchanged drug.
• Clearance: * 2.5 - 10.9 L/h [Following oral inhalation 10 mg]; * 5.3 L/h [Normal renal function receiving IV single dose of 4 mg or 2 mg]; * 2.7 L/h [Patients with mild and moderate renal impairement receiving IV single dose of 4 mg or 2 mg]; * 0.8 L/h [Patients with severe renal impairement receiving IV single dose of 4 mg or 2 mg]
• References: Meindl P, Bodo G, Palese P, Schulman J, Tuppy H: Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology. 1974 Apr;58(2):457-63. [Pubmed] ; von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, et al.: Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature. 1993 Jun 3;363(6428):418-23. [Pubmed] ; Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T: Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases. Antimicrob Agents Chemother. 2008 Aug 11. [Pubmed] ; Sugaya N, Tamura D, Yamazaki M, Ichikawa M, Kawakami C, Kawaoka Y, Mitamura K: Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis. 2008 Aug 1;47(3):339-45. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Meindl P, Bodo G, Palese P, Schulman J, Tuppy H: Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology. 1974 Apr;58(2):457-63. Pubmed
• von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, et al.: Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature. 1993 Jun 3;363(6428):418-23. Pubmed
• Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T: Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases. Antimicrob Agents Chemother. 2008 Aug 11. Pubmed
• Sugaya N, Tamura D, Yamazaki M, Ichikawa M, Kawakami C, Kawaoka Y, Mitamura K: Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis. 2008 Aug 1;47(3):339-45. Pubmed