[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl]methanol

• ChemBase编号: 920
• 分子式: C14H18N6O
• 平均质量: 286.33232
• 单一同位素质量: 286.15420923
• SMILES: c12c(n(cn2)[C@@H]2C[C@@H](C=C2)CO)nc(nc1NC1CC1)N
• Canonical SMILES: OC[C@@H]1C=C[C@@H](C1)n1cnc2c1nc(N)nc2NC1CC1
• InChI: InChI=1S/C14H18N6O/c15-14-18-12(17-9-2-3-9)11-13(19-14)20(7-16-11)10-4-1-8(5-10)6-21/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19)/t8-,10+/m1/s1
• InChIKey: MCGSCOLBFJQGHM-SCZZXKLOSA-N

名称和登记号

名称

• IUPAC标准名: [(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl]methanol
• IUPAC传统名: abacavir; @abacavir; [(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl]methanol
• 商标名: Ziagen
• 别名: (1S,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol; (1S-cis)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol; 1592U89; Abacavir(see A105000); ABC; Abacavir; Ziagen; Abacavir

登记号

• CAS号: 136470-78-5
• PubChem SID: 46505718; 160964383
• PubChem CID: 441300

理论计算性质

JChem

• Acid pKa: 15.406518
• 质子受体: 6
• 质子供体: 3
• LogD (pH = 5.5): 0.38658103
• LogD (pH = 7.4): 0.38677147
• Log P: 0.3867739
• 摩尔折射率: 82.6231 cm^3
• 极化性: 29.981058 Å^3
• 极化表面积: 101.88 Å^2
• 可自由旋转的化学键: 4
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 0.61
• LOG S: -2.37
• 溶解度: 1.21e+00 g/l

分子性质

理化性质

• 溶解度: 77 mg/mL (sulfate salt); DMSO; Methanol
• 疏水性(logP): 1.1

安全信息

• 保存条件: Refrigerator

药理学性质

• 生物活性机理: HIV reverse transcriptase inhibitor

产品相关信息

• 应用领域: Antiviral agent; Shows anti-HIV activity

详细说明

DrugBank - DB01048

• Drug Groups: approved; investigational
• Description: Abacavir (ABC) is a powerful nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. [Wikipedia]
• Indication: For the treatment of HIV-1 infection, in combination with other antiretroviral agents.
• Pharmacology: Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Abacavir 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: Some myocardial degeneration has been noticed in rats and mice
• Affected Organisms: Human Immunodeficiency Virus
• Biotransformation: Hepatic, by alcohol dehydrogenase and glucuronosyltransferase to a 5′-carboxylic acid metabolite and 5′-glucuronide metabolite, respectively. These metabolites have no antiviral activity. Abacavir is not significantly metabolized by cytochrome P450 enzymes.
• Absorption: Rapid and extensive after oral administration (83% bioavailability)
• Half Life: 1.54 ± 0.63 hours
• Protein Binding: Moderate (approximately 50%)
• Elimination: Elimination of abacavir was quantified in a mass balance study following administration of a 600-mg dose of 14C-abacavir: 99% of the radioactivity was recovered, 1.2% was excreted in the urine as abacavir, 30% as the 5′-carboxylic acid metabolite, 36% as the 5′-glucuronide metabolite, and 15% as unidentified minor metabolites in the urine. Fecal elimination accounted for 16% of the dose. Fecal elimination accounted for 16% of the dose. Renal excretion of unchanged abacavir is a minor route of elimination in humans.
• Distribution: * 0.86 ± 0.15 L/kg
• Clearance: * 0.80 +/- 0.24 L/hr/kg [asymptomatic, HIV-1-infected adult patients receiving single (IV dose of 150?mg]
• References: Zucman D, Truchis P, Majerholc C, Stegman S, Caillat-Zucman S: Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. J Acquir Immune Defic Syndr. 2007 May 1;45(1):1-3. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Toronto Research Chemicals - A104990

A nucleoside reverse transcriptase inhibitor (NRTI).

参考文献

• Zucman D, Truchis P, Majerholc C, Stegman S, Caillat-Zucman S: Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. J Acquir Immune Defic Syndr. 2007 May 1;45(1):1-3. Pubmed
• Hanumegowda, U., et al.: Chem. Res. Toxicol., 23, 749 (2010)
• Prasse, C., et al.: Environ. Sci. Technol., 44, 1728 (2010)
• Eur. Pat., 1991, Wellcome Foundation, 434 450; CA, 115, 208462c, (synth, pharmacol)
• Crimmins, M.T. et al., J.O.C., 1996, 61, 4192-4193, (synth, pmr, cmr, ir)
• Pat. Coop. Treaty (WIPO), 1996, Wellcome Foundation, 96 06 844; CA, 125, 41774y, (succinate)
• Daluge, S.M., Antimicrob. Agents Chemother., 1997, 41, 1082-1093; 1099-1107, (pharmacol, activity)
• Foster, R.H. et al., Drugs, 1998, 55, 729-736, (rev)
• Graul, A. et al., Drugs of the Future, 1998, 23, 1155-1167, (abacavir sulfate)
• Olivo, H.F., J.C.S. Perkin 1, 1998, 391, 392, (synth, bibl)
• Pat. Coop. Treaty (WIPO), 1998, Glaxo, 98 52 949; CA, 130, 38645e, (abacavir sulfate)
• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 602
• Moyle, J.G., Curr. Opin. Infect. Dis., 2000, 13, 19
• Hervey, P.S. et al., Drugs, 2000, 60, 447-479, (rev)
• Daluge, S.M. et al., Nucleosides Nucleotides, 2000, 19, 297-327, (synth)