(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide

• ChemBase编号: 105
• 分子式: C32H45N3O4S
• 平均质量: 567.7824
• 单一同位素质量: 567.31307794
• SMILES: S(C[C@H](NC(=O)c1c(c(O)ccc1)C)[C@H](O)CN1C[C@@H]2[C@H](C[C@H]1C(=O)NC(C)(C)C)CCCC2)c1ccccc1
• Canonical SMILES: O[C@@H]([C@@H](NC(=O)c1cccc(c1C)O)CSc1ccccc1)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C
• InChI: InChI=1S/C32H45N3O4S/c1-21-25(15-10-16-28(21)36)30(38)33-26(20-40-24-13-6-5-7-14-24)29(37)19-35-18-23-12-9-8-11-22(23)17-27(35)31(39)34-32(2,3)4/h5-7,10,13-16,22-23,26-27,29,36-37H,8-9,11-12,17-20H2,1-4H3,(H,33,38)(H,34,39)/t22-,23+,26-,27-,29+/m0/s1
• InChIKey: QAGYKUNXZHXKMR-HKWSIXNMSA-N

名称和登记号

名称

• IUPAC标准名: (3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide
• IUPAC传统名: nelfinavir
• 商标名: Viracept
• 别名: 1UN; Nelfinavir mesylate; NFV; NLF; AG1343; Nelfinavir

登记号

• CAS号: 159989-64-7
• PubChem SID: 46507719; 160963568
• PubChem CID: 64143

理论计算性质

JChem

• Acid pKa: 9.317774
• 质子受体: 5
• 质子供体: 4
• LogD (pH = 5.5): 2.3172343
• LogD (pH = 7.4): 4.085969
• Log P: 4.718828
• 摩尔折射率: 162.6745 cm^3
• 极化性: 63.215218 Å^3
• 极化表面积: 101.9 Å^2
• 可自由旋转的化学键: 10
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 4.61
• LOG S: -5.47
• 溶解度: 1.91e-03 g/l

分子性质

理化性质

• 溶解度: Slightly soluble
• 疏水性(logP): 6

详细说明

DrugBank - DB00220

• Drug Groups: approved
• Description: A potent HIV-1 protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [PubChem]
• Indication: Used in combination with other antiviral drugs in the treatment of HIV in both adults and children.
• Pharmacology: Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
• Toxicity: Oral LD₅₀ is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.
• Affected Organisms: Human Immunodeficiency Virus
• Biotransformation: Primarily hepatic via cytochrome P450 (CYP450) enzymes. CYP3A and CYP2C19 appear to be the predominant enzymes that metabolize nelfinavir in humans. One major and several minor metabolites are found in plasma; the major oxidative metabolite has in vitro antiviral activity comparable to that of the parent drug.
• Absorption: Well absorbed following oral administration.
• Half Life: 3.5 - 5 hours
• Protein Binding: >98%
• Elimination: The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1–2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.
• Distribution: * 2 to 7 L/kg
• References: Kaldor SW, Kalish VJ, Davies JF 2nd, Shetty BV, Fritz JE, Appelt K, Burgess JA, Campanale KM, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH: Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

参考文献

• Kaldor SW, Kalish VJ, Davies JF 2nd, Shetty BV, Fritz JE, Appelt K, Burgess JA, Campanale KM, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH: Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85. Pubmed