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

• ChemBase编号: 531
• 分子式: C10H12N2O4
• 平均质量: 224.21328
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
• IUPAC传统名: stavudine
• 商标名: Zerit; Zerit XR; Zerut XR
• 别名: 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

登记号

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

理论计算性质

JChem

• Acid pKa: 9.952853
• 质子受体: 4
• 质子供体: 2
• LogD (pH = 5.5): -0.23182122
• LogD (pH = 7.4): -0.23300652
• Log P: -0.2318061
• 摩尔折射率: 55.3163 cm^3
• 极化性: 21.057823 Å^3
• 极化表面积: 78.87 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -0.73
• LOG S: -0.74
• 溶解度: 4.05e+01 g/l

分子性质

理化性质

• 溶解度: 5-10 g/100 mL at 21 oC; Chloroform; DMSO; Ethanol; Methanol
• 外观: White to Off-White Solid
• 熔点: 165-166°C
• 疏水性(logP): -0.488; -0.8

安全信息

• 保存条件: -20°C Freezer
• RTECS编号: XP2075000
• 德国WGK号: 2
• 个人保护装置: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• 保存温度: -20°C

产品相关信息

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

详细说明

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.

参考文献

• 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)