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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H35N3O6S
Molecular Weight 505.627
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMPRENAVIR

SMILES

CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CCOC2)S(=O)(=O)C3=CC=C(N)C=C3

InChI

InChIKey=YMARZQAQMVYCKC-OEMFJLHTSA-N
InChI=1S/C25H35N3O6S/c1-18(2)15-28(35(31,32)22-10-8-20(26)9-11-22)16-24(29)23(14-19-6-4-3-5-7-19)27-25(30)34-21-12-13-33-17-21/h3-11,18,21,23-24,29H,12-17,26H2,1-2H3,(H,27,30)/t21-,23-,24+/m0/s1

HIDE SMILES / InChI

Molecular Formula C25H35N3O6S
Molecular Weight 505.627
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Amprenavir is an inhibitor of HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles. Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). Fosamprenavir (GW433908, Lexiva, Telzir) is an oral prodrug of amprenavir, with a reduced daily pill burden. The use of protease inhibitors has also been associated with dyslipidemia and an increased risk of cardiovascular disease. Amprenavir activates Pregnane X receptor to mediate dyslipidemia.

CNS Activity

Originator

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AGENERASE
PubMed

PubMed

TitleDatePubMed
Four new antiretroviral medications will soon offer more options to HIV patients.
1998 Jul-Aug
Structural and kinetic analyses of the protease from an amprenavir-resistant human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and resensitized to amprenavir.
2000 Aug
BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents.
2000 Aug
A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir.
2000 May
Inhibition of HIV-1 protease by a boron-modified polypeptide.
2000 Oct 1
Early detection of mixed mutations selected by antiretroviral agents in HIV-infected primary human lymphocytes.
2001
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.
2001 Apr 15
[Determining resistance in HIV therapy. Careful interpretation only].
2001 Apr 2
Antiretrovirals: simultaneous determination of five protease inhibitors and three nonnucleoside transcriptase inhibitors in human plasma by a rapid high-performance liquid chromatography--mass spectrometry assay.
2001 Aug
Antiviral drugs: current state of the art.
2001 Aug
Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection.
2001 Dec
[Resistance to protease inhibitors].
2001 Feb
Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.
2001 Feb
[Pharmacological study and clinical effect of HIV protease inhibitor amprenavir].
2001 Jan
New developments in anti-HIV chemotherapy.
2001 Jan-Feb
Structure-based design of non-peptide HIV protease inhibitors.
2001 Jan-Feb
Capillary electrophoretic separation of protease inhibitors used in human immunodeficiency virus therapy.
2001 Jul 13
High-performance liquid chromatographic assay to determine the plasma levels of HIV-protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir and saquinavir) and the non-nucleoside reverse transcriptase inhibitor (nevirapine) after liquid-liquid extraction.
2001 Jul 15
Synthesis of a chiral aziridine derivative as a versatile intermediate for HIV protease inhibitors.
2001 Jul 26
Antiretroviral activity and safety of abacavir in combination with selected HIV-1 protease inhibitors in therapy-naive HIV-1-infected adults.
2001 Jun
Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.
2001 Jun 15
Effect of reduced-dose amprenavir in combination with lopinavir on plasma levels of amprenavir in patients infected with HIV.
2001 Mar
Increased turnover of CCR5+ and redistribution of CCR5- CD4 T lymphocytes during primary human immunodeficiency virus type 1 infection.
2001 Mar 1
Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir-experienced subjects: AIDS Clinical Trials Group protocol 373.
2001 Mar 1
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.
2001 Mar 30
Drifting agenda for federal treatment research.
2001 May
Pharmacokinetics and safety of amprenavir and ritonavir following multiple-dose, co-administration to healthy volunteers.
2001 May 25
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.
2001 May 5
[Drug interactions with antiretroviral agents].
2001 May-Jun
New developments in anti-HIV chemotherapy.
2001 Nov
Anti-human immunodeficiency virus drugs are ineffective against Pneumocystis carinii in vitro and in vivo.
2001 Nov 15
In vitro activity of amprenavir against Pneumocystis carinii.
2001 Sep
Mismatched double-stranded RNA (polyI-polyC(12)U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in vitro.
2001 Sep
Amping amprenavir with ritonavir.
2001 Spring
Retroviral proteases.
2002
Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium antagonist.
2002
New dosing regimen approved.
2002 Apr
Simultaneous determination of the six HIV protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) plus M8 nelfinavir metabolite and the nonnucleoside reverse transcription inhibitor efavirenz in human plasma by solid-phase extraction and column liquid chromatography.
2002 Apr
A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site.
2002 Feb
Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of a high multitude of HIV-1 resistance against protease inhibitors.
2002 Feb 22
Central nervous system toxicity and amprenavir oral solution.
2002 Jan
Clinical pharmacology and pharmacokinetics of amprenavir.
2002 Jan
Unfavourable interaction of amprenavir and lopinavir in combination with ritonavir?
2002 Jan 25
Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure.
2002 Jul
Lipodystrophy update.
2002 Mar
Efavirenz-induced skin eruption and successful desensitization.
2002 Mar
FDA approves new dosing for amprenavir and ritonavir combination.
2002 Mar 8
Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection.
2002 Mar 8
Patents

Sample Use Guides

In Vivo Use Guide
Adults: The recommended oral dose of AGENERASE Capsules for adults is 1200 mg (eight 150-mg capsules) twice daily in combination with other antiretroviral agents. Concomitant Therapy: If AGENERASE and ritonavir are used in combination, the recommended dosage regimens are: AGENERASE 1200 mg with ritonavir 200 mg once daily or AGENERASE 600 mg with ritonavir 100 mg twice daily. Pediatric Patients: For adolescents (13 to 16 years), the recommended oral dose of AGENERASE Capsules is 1200 mg (eight 150-mg capsules) twice daily in combination with other antiretroviral agents. For patients between 4 and 12 years of age or for patients 13 to 16 years of age with weight of <50 kg, the recommended oral dose of AGENERASE Capsules is 20 mg/kg twice daily or 15 mg/kg 3 times daily (to a maximum daily dose of 2400 mg) in combination with other antiretroviral agents.
Route of Administration: Oral
In Vitro Use Guide
The in vitro antiviral activity of amprenavir was evaluated against HIV-1 IIIB in both acutely and chronically infected lymphoblastic cell lines (MT-4, CEM-CCRF, 43 H9) and in peripheral blood lymphocytes. The 50% inhibitory concentration (IC50) of amprenavir ranged from 0.012 to 0.08 µM in acutely infected cells and was 0.41 µM in chronically infected cells (1 µM = 0.50 mcg/mL).
Substance Class Chemical
Created
by admin
on Mon Oct 21 19:51:19 UTC 2019
Edited
by admin
on Mon Oct 21 19:51:19 UTC 2019
Record UNII
5S0W860XNR
Record Status Validated (UNII)
Record Version
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Name Type Language
AMPRENAVIR
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
AMPRENAVIR [EMA EPAR]
Common Name English
VX-478
Code English
AMPRENAVIR [VANDF]
Common Name English
AMPRENAVIR [MART.]
Common Name English
KVX-478
Code English
(3S-(3R*(1R*,2S*)))-(3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL) TETRAHYDRO-3-FURANYL CARBAMATE
Common Name English
AMPRENAVIR [MI]
Common Name English
AMPRENAVIR [HSDB]
Common Name English
AMPRENAVIR [WHO-DD]
Common Name English
141 W94
Code English
AMPRENAVIR [ORANGE BOOK]
Common Name English
J05AE05
Code English
AMPRENAVIR [USAN]
Common Name English
AGENERASE
Brand Name English
AMPRENAVIR [JAN]
Common Name English
AMPRENAVIR [INN]
Common Name English
141W94
Code English
(3S)-TETRAHYDRO-3-FURYL ((.ALPHA.S)-.ALPHA.-((1R-1-HYDROXY-2-(N1-ISOBUTYLSULFANILAMIDO)ETHYL)PHENETHYL)CARBAMATE
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS AGENERASE (WITHDRAWN: HIV INFECTIONS)
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
WHO-ATC J05AE05
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
NDF-RT N0000175889
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
NCI_THESAURUS C97366
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
NDF-RT N0000000246
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
WHO-VATC QJ05AE05
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
LIVERTOX 53
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
Code System Code Type Description
NDF-RT
N0000182141
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
NDF-RT
N0000185506
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY Cytochrome P450 3A4 Inducers [MoA]
MESH
C095108
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
RXCUI
228656
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY RxNorm
PUBCHEM
65016
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
NCI_THESAURUS
C28824
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
INN
7751
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
EPA CompTox
161814-49-9
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
DRUG BANK
DB00701
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
ChEMBL
CHEMBL116
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
WIKIPEDIA
AMPRENAVIR
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
MERCK INDEX
M1855
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY Merck Index
NDF-RT
N0000191264
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY P-Glycoprotein Inducers [MoA]
CAS
161814-49-9
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
EVMPD
SUB00511MIG
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
HSDB
161814-49-9
Created by admin on Mon Oct 21 19:51:19 UTC 2019 , Edited by admin on Mon Oct 21 19:51:19 UTC 2019
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC