1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

• ChemBase ID: 531
• Molecular Formular: C10H12N2O4
• Molecular Mass: 224.21328
• Monoisotopic Mass: 224.07970687
• SMILES: O1[C@@H](n2cc(c(=O)[nH]c2=O)C)C=C[C@H]1CO
• Canonical SMILES: Cc1cn([C@@H]2O[C@@H](C=C2)CO)c(=O)[nH]c1=O
• InChI: InChI=1S/C10H12N2O4/c1-6-4-12(10(15)11-9(6)14)8-3-2-7(5-13)16-8/h2-4,7-8,13H,5H2,1H3,(H,11,14,15)/t7-,8+/m0/s1
• InChIKey: XNKLLVCARDGLGL-JGVFFNPUSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
• IUPAC Traditional name: stavudine
• Brand Name: Zerit; Zerit XR; Zerut XR
• Synonyms: 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione; STV; Estavudina [INN-Spanish]; Sanilvudine; Stavudine [Usan:Ban:Inn]; Stavudinum [INN-Latin]; 2',3'-Didehydro-3'-deoxythimidine; 3'-Deoxy-2'-thymidinene; stavudine; Stavudine; 2',3'-Didehydro-3'-deoxythymidine, 3'-Deoxy-2'-thymidinene; 3'-Deoxy-2',3'-didehydrothymidine; Avostav; D4t, BMY-27857, Zerit; NSC 163661; Virostav; Sanilvudine; 1-((2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione; 1-(2,3-Dideoxy-β-D-glycero-pent-2-enofuranosyl)thymine; 2′,3′-Anhydrothymidine; d4T; 2′,3′-Didehydro-3′-deoxythymidine

Database IDs

• CAS Number: 3056-17-5
• MDL Number: MFCD00132921
• PubChem SID: 160963994; 46506943; 24278356
• PubChem CID: 18283

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.952853
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): -0.23182122
• LogD (pH = 7.4): -0.23300652
• Log P: -0.2318061
• Molar Refractivity: 55.3163 cm^3
• Polarizability: 21.057823 Å^3
• Polar Surface Area: 78.87 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -0.73
• LOG S: -0.74
• Solubility (Water): 4.05e+01 g/l

PROPERTIES

Physical Property

• Solubility: 5-10 g/100 mL at 21 oC; Chloroform; DMSO; Ethanol; Methanol
• Apperance: White to Off-White Solid
• Melting Point: 165-166°C
• Hydrophobicity(logP): -0.488; -0.8

Safety Information

• Storage Condition: -20°C Freezer
• RTECS: XP2075000
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: -20°C

Product Information

• Purity: ≥98% (TLC); 95%; 98%
• Empirical Formula (Hill Notation): C10H12N2O4

DETAILS

DrugBank - DB00649

• Drug Groups: approved; investigational
• Description: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [PubChem]
• Indication: For the treatment of human immunovirus (HIV) infections.
• Pharmacology: Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.
• Toxicity: Side effects include peripheral neuropathy tingling, burning, numbness, or pain in the hands or feet), fatal lactic acidosis has been reported in patients treated with stavudine (ZERIT) in combination with other antiretroviral agents, severe liver enlargement, inflammation (pain and swelling) of the liver, and liver failure.
• Affected Organisms: Human Immunodeficiency Virus
• Biotransformation: Phosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase.
• Absorption: Following oral administration, stavudine is rapidly absorbed (bioavailability is 68-104%).
• Half Life: 0.8-1.5 hours (in adults)
• Protein Binding: Negligible
• Distribution: * 46 ± 21 L
• Clearance: * Renal cl=272 mL/min [Healthy subjects receiving 80 mg PO]; * 594 +/- 164 mL/min [HIV-infected adult and pediatric patients following 1-hour IV infusion]; * 9.75 +/- 3.76 mL/min/kg [HIV- Exposed or -Infected Pediatric Patients(Age 5 weeks – 15 years) following 1-hour IV infusion]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Sigma Aldrich - D1413

Biochem/physiol Actions
Nucleoside analog which inhibits HIV replication in vitro.

Toronto Research Chemicals - S685250

Used as an antiviral. A reverse transcriptase inhibitor.

REFERENCES

• Mansuri, M.M., et al.: Antimicrob. Ag. Chemother., 34, 637 (1990)
• Cretton, E.M., et al.: Antimicrob. Ag. Chemother., 37, 1816 (1990)
• Browne, M.J., et al.: J. Infec. Dis., 167, 21 (1993)