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

• ChemBase ID: 105
• Molecular Formular: C32H45N3O4S
• Molecular Mass: 567.7824
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide
• IUPAC Traditional name: nelfinavir
• Brand Name: Viracept
• Synonyms: 1UN; Nelfinavir mesylate; NFV; NLF; AG1343; Nelfinavir

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.317774
• H Acceptors: 5
• H Donor: 4
• LogD (pH = 5.5): 2.3172343
• LogD (pH = 7.4): 4.085969
• Log P: 4.718828
• Molar Refractivity: 162.6745 cm^3
• Polarizability: 63.215218 Å^3
• Polar Surface Area: 101.9 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.61
• LOG S: -5.47
• Solubility (Water): 1.91e-03 g/l

PROPERTIES

Physical Property

• Solubility: Slightly soluble
• Hydrophobicity(logP): 6

DETAILS

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

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