2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one

• ChemBase ID: 325
• Molecular Formular: C12H15N5O3
• Molecular Mass: 277.2792
• Monoisotopic Mass: 277.11748937
• SMILES: O[C@@H]1[C@H](C(=C)[C@@H](n2c3[nH]c(nc(=O)c3nc2)N)C1)CO
• Canonical SMILES: OC[C@@H]1[C@@H](O)C[C@@H](C1=C)n1cnc2c1[nH]c(N)nc2=O
• InChI: InChI=1S/C12H15N5O3/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20)/t6-,7-,8-/m0/s1
• InChIKey: QDGZDCVAUDNJFG-FXQIFTODSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one
• IUPAC Traditional name: baraclude
• Brand Name: Baraclude
• Synonyms: entecavir; Entecavir

Database IDs

• CAS Number: 142217-69-4
• PubChem SID: 46504864; 160963788
• PubChem CID: 153941

CALCULATED PROPERTIES

JChem

• Acid pKa: 8.0033045
• H Acceptors: 7
• H Donor: 4
• LogD (pH = 5.5): -1.4469311
• LogD (pH = 7.4): -1.5362015
• Log P: -1.4446591
• Molar Refractivity: 71.0008 cm^3
• Polarizability: 26.432161 Å^3
• Polar Surface Area: 125.76 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -0.81
• LOG S: -1.62
• Solubility (Water): 6.59e+00 g/l

PROPERTIES

Physical Property

• Solubility: Slightly soluble (2.4 mg/mL at pH 7.9, 25oC)
• Hydrophobicity(logP): -0.8

DETAILS

DrugBank - DB00442

• Drug Groups: approved; investigational
• Description: Entecavir is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude (BMS).; ; Entecavir is a guanine analogue that inhibits all three steps in the viral replication process, and the manufacturer claims that it is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir). It was approved by the U.S. Food and Drug Administration (FDA) in March 2005.
• Indication: For the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
• Pharmacology: Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It is designed to selectively inhibit the Hepatitis B virus, blocking all three steps in the replication process. Entecavir is more efficient than an older Hepatitis B drug, lamivudine.
• Toxicity: Healthy subjects who received single entecavir doses up to 40 mg or multiple doses up to 20 mg/day for up to 14 days had no increase in or unexpected adverse events. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
• Affected Organisms: Hepatitis B virus
• Biotransformation: Entecavir is not a substrate, inhibitor, or inducer of the cytochrome P450 (CYP450) enzyme system. Entecavir is efficiently phosphorylated to the active triphosphate form.
• Absorption: Absorption Following oral administration in healthy subjects, entecavir peak plasma concentrations occurred between 0.5 and 1.5 hours. In healthy subjects, the bioavailability of the tablet is 100% relative to the oral solution.
• Half Life: After reaching peak concentration, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of approximately 128-149 hours. The phosphorylated metabolite has a half-life of 15 hours.
• Protein Binding: Binding of entecavir to human serum proteins in vitro is approximately 13%.
• Clearance: * renal cl=383.2 +/- 101.8 mL/min [Unimpaired renal function]; * renal cl=197.9 +/- 78.1 mL/min [Mild impaired renal function]; * renal cl=135.6 +/- 31.6 mL/min [Moderate impaired renal function]; * renal cl=40.3 +/- 10.1 mL/min [severe impaired renal function]; * apparent oral cl=588.1 +/- 153.7 mL/min [Unimpaired renal function]; * apparent oral cl=309.2 +/- 62.6 mL/min [Mild impaired renal function]; * apparent oral cl=226.3 +/- 60.1 mL/min [Moderate impaired renal function]; * apparent oral cl=100.6 +/- 29.1 mL/min [severe impaired renal function]; * apparent oral cl=50.6 +/- 16.5 mL/min [severe impaired renal function amnaged with Hemodialysis]; * apparent oral cl=35.7 +/- 19.6 mL/min [severe impaired renal function amnaged with CAPD]
• External Links: Wikipedia; RxList; Drugs.com