methyl N-[(1S)-1-{N'-[(2S,3S)-2-hydroxy-3-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanamido]-4-phenylbutyl]-N'-{[4-(pyridin-2-yl)phenyl]methyl}hydrazinecarbonyl}-2,2-dimethylpropyl]carbamate

• ChemBase ID: 943
• Molecular Formular: C38H52N6O7
• Molecular Mass: 704.85548
• Monoisotopic Mass: 704.38974803
• SMILES: O[C@H]([C@@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)Cc1ccccc1)CN(NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)Cc1ccc(cc1)c1ncccc1
• Canonical SMILES: COC(=O)N[C@@H](C(C)(C)C)C(=O)NN(Cc1ccc(cc1)c1ccccn1)C[C@@H]([C@H](Cc1ccccc1)NC(=O)[C@H](C(C)(C)C)NC(=O)OC)O
• InChI: InChI=1S/C38H52N6O7/c1-37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47)/t29-,30-,31+,32+/m0/s1
• InChIKey: AXRYRYVKAWYZBR-GASGPIRDSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: methyl N-[(1S)-1-{N'-[(2S,3S)-2-hydroxy-3-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanamido]-4-phenylbutyl]-N'-{[4-(pyridin-2-yl)phenyl]methyl}hydrazinecarbonyl}-2,2-dimethylpropyl]carbamate; methyl N-[(1S)-1-{[(2S,3S)-3-hydroxy-4-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethyl-N'-{[4-(pyridin-2-yl)phenyl]methyl}butanehydrazido]-1-phenylbutan-2-yl]carbamoyl}-2,2-dimethylpropyl]carbamate
• IUPAC Traditional name: methyl N-[(1S)-1-{N'-[(2S,3S)-2-hydroxy-3-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanamido]-4-phenylbutyl]-N'-{[4-(pyridin-2-yl)phenyl]methyl}hydrazinecarbonyl}-2,2-dimethylpropyl]carbamate; atazanavir
• Brand Name: Latazanavir; Reyataz; Zrivada
• Synonyms: 3,12-Bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-[[4-(2-pyridinyl)phenyl]methyl]-dimethyl Ester; (3S,8S, 9S, 12S)-2,5,6,13-Pentaazatetradecanedioic Acid; CGP-73547; ATV; ATZ; BMS-232632; Atazanavir sulfate; atazanavir; Atazanavir; Reyataz; Atazanavir(BMS-232632)

Database IDs

• CAS Number: 198904-31-3
• PubChem SID: 46508504; 160964406
• PubChem CID: 148192

CALCULATED PROPERTIES

JChem

• Acid pKa: 11.919422
• H Acceptors: 7
• H Donor: 5
• LogD (pH = 5.5): 4.5060835
• LogD (pH = 7.4): 4.5393934
• Log P: 4.5398483
• Molar Refractivity: 191.8025 cm^3
• Polarizability: 76.91037 Å^3
• Polar Surface Area: 171.22 Å^2
• Rotatable Bonds: 18
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.08
• LOG S: -5.33
• Solubility (Water): 3.27e-03 g/l

PROPERTIES

Physical Property

• Solubility: Free base slightly soluble (4-5 mg/mL); Methanol
• Apperance: Off-White Solid
• Melting Point: 207-209°C
• Hydrophobicity(logP): 4.5

Safety Information

• Storage Condition: -20°C; -20°C Freezer

Pharmacology Properties

• Target: Proteasome

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB01072

• Drug Groups: approved; investigational
• Description: Atazanavir (formerly known as BMS-232632) is an antiretroviral drug of the protease inhibitor (PI) class. Like other antiretrovirals, it is used to treat infection of human immunodeficiency virus (HIV). Atazanavir is distinguished from other PIs in that it can be given once-daily (rather than requiring multiple doses per day) and has lesser effects on the patient's lipid profile (the amounts of cholesterol and other fatty substances in the blood). Like other protease inhibitors, it is used only in combination with other HIV medications. The U.S. Food and Drug Administration (FDA) approved atazanavir on June 20, 2003. [Wikipedia]
• Indication: Used in combination with other antiretroviral agents for the treatment of HIV-1 infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.
• Pharmacology: Atazanavir (ATV) is an azapeptide HIV-1 protease inhibitor (PI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). 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. Atazanavir 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. Atazanivir is pharmacologically related but structurally different from other protease inhibitors and other currently available antiretrovirals.
• Affected Organisms: Human Immunodeficiency Virus
• Biotransformation: Atazanavir is extensively metabolized in humans, primarily by the liver. The major biotransformation pathways of atazanavir in humans consisted of monooxygenation and dioxygenation. Other minor biotransformation pathways for atazanavir or its metabolites consisted of glucuronidation, N-dealkylation, hydrolysis, and oxygenation with dehydrogenation. In vitro studies using human liver microsomes suggested that atazanavir is metabolized by CYP3A.
• Absorption: Atazanavir is rapidly absorbed with a T_max of approximately 2.5 hours. Administration of atazanavir with food enhances bioavailability and reduces pharmacokinetic variability. Oral bioavailability is 60-68%.
• Half Life: Elimination half-life in adults (healthy and HIV infected) is approximately 7 hours (following a 400 mg daily dose with a light meal). Elimination half-life in hepatically impaired is 12.1 hours (following a single 400 mg dose).
• Protein Binding: 86% bound to human serum proteins (alpha-1-acid glycoprotein and albumin). Protein binding is independent of concentration.
• References: Croom KF, Dhillon S, Keam SJ: Atazanavir: a review of its use in the management of HIV-1 infection. Drugs. 2009 May 29;69(8):1107-40. doi: 10.2165/00003495-200969080-00009. [Pubmed] ; von Hentig N: Atazanavir/ritonavir: a review of its use in HIV therapy. Drugs Today (Barc). 2008 Feb;44(2):103-32. [Pubmed] ; Swainston Harrison T, Scott LJ: Atazanavir: a review of its use in the management of HIV infection. Drugs. 2005;65(16):2309-36. [Pubmed] ; Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. [Pubmed] ; Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir] Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. [Pubmed] ; Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1457

Research Area: Infection
Biological Activity:
Atazanavir sulfate(BMS-232632-05) is a sulfate salt form of atazanavir (BMS-232632) that is an highly potent HIV protease inhibitor with an EC50 and EC90 of 2.6~5.3 nM and 9~15 nM in cell culture. Atazanavir (BMS-232632) is generally more potent than the five currently approved HIV-1 Prt inhibitors. Atazanavir (BMS-232632) inhibited the proteolytic cleavage of the viral gag precursor p55 polyprotein in a dose-dependent manner, with a EC50 of approximately 47 nM. Furthermore, Atazanavir (BMS-232632) is highly selective for HIV-1 Prt and exhibits cytotoxicity only at concentrations 6,500- to 23,000-fold higher than that required for anti-HIV activity. Atazanavir (BMS-232632) may be an effective HIV-1 inhibitor that may be utilized in a variety of different drug combinations. [1][2]References on Atazanavir sulfate[] ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 2000, 44:2093–2099[] Organic Process Research & Development, 2002, 6:323−328

Toronto Research Chemicals - A790051

Atazanavir is a novel azapeptide HIV protease inhibitor (PI). Antiviral.

REFERENCES

• Croom KF, Dhillon S, Keam SJ: Atazanavir: a review of its use in the management of HIV-1 infection. Drugs. 2009 May 29;69(8):1107-40. doi: 10.2165/00003495-200969080-00009. Pubmed
• von Hentig N: Atazanavir/ritonavir: a review of its use in HIV therapy. Drugs Today (Barc). 2008 Feb;44(2):103-32. Pubmed
• Swainston Harrison T, Scott LJ: Atazanavir: a review of its use in the management of HIV infection. Drugs. 2005;65(16):2309-36. Pubmed
• Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. Pubmed
• Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir] Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. Pubmed
• Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. Pubmed
• http://en.wikipedia.org/wiki/Atazanavir
• Musial, B.L., et al.: Am. J. Health Syst. Pharm., 61, 1365 (13)
• Wood, R., et al.: J. Acquir. Immune Defic. Syndr., 36, 684 (13)
• Palella, F.J. Jr., et al.: N. Engl. J. Med., 338(13)
• 853 (13)
• Nolan, D., et al.: Drugs, 63(13)
• 2555 (13)