アンプレナビル
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/19 19:33:05」(JST)
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This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2009) |
Amprenavir
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| Systematic (IUPAC) name |
| (3S)-oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-1-phenylbutan-2-yl]carbamate |
| Clinical data |
| Trade names |
Agenerase |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a699051 |
| Licence data |
EMA:Link, US FDA:link |
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Pregnancy
category
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- US: C (Risk not ruled out)
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Routes of
administration
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oral |
| Pharmacokinetic data |
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Protein binding
|
90% |
| Metabolism |
hepatic |
| Half-life |
7.1-10.6 hours |
| Excretion |
<3% renal |
| Identifiers |
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CAS Registry Number
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161814-49-9 Y |
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ATC code
|
J05AE05 |
| PubChem |
CID: 65016 |
| DrugBank |
DB00701 Y |
| ChemSpider |
58532 Y |
| UNII |
5S0W860XNR Y |
| KEGG |
D00894 Y |
| ChEBI |
CHEBI:40050 Y |
| ChEMBL |
CHEMBL116 Y |
| NIAID ChemDB |
006080 |
| Chemical data |
| Formula |
C25H35N3O6S |
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Molecular mass
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505.628 g/mol |
SMILES
- O=C(O[C@H]1CCOC1)N[C@@H](Cc2ccccc2)[C@H](O)CN(CC(C)C)S(=O)(=O)c3ccc(N)cc3
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InChI
-
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 Y
Key:YMARZQAQMVYCKC-OEMFJLHTSA-N Y
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| Y (what is this?) (verify) |
Amprenavir (Agenerase, GlaxoSmithKline) is a protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200 mg, delivered in eight very large gel capsules.
Production of amprenavir was discontinued by the manufacturer December 31, 2004; a prodrug version (fosamprenavir) is available.
HIV-1 Protease dimer with Amprenavir (sticks) bound in the active site. PDB entry
3nu3 [1]
Contents
- 1 Background
- 2 Synthesis
- 3 See also
- 4 External links
Background
Research aimed at development of renin inhibitors as potential antihypertensive agents had led to the discovery of compounds that blocked the action of this peptide cleaving enzyme. The amino acid sequence cleaved by renin was found to be fortuitously the same as that required to produce the HIV peptide coat. Structure–activity studies on renin inhibitors proved to be of great value for developing HIV protease inhibitors. Incorporation of an amino alcohol moiety proved crucial to inhibitory activity for many of these agents. This unit is closely related to the one found in the statine, an unusual amino acid that forms part of the pepstatin, a fermentation product that inhibits protease enzymes.
Synthesis
[2]
R.D. Tung, M.A. Murcko, G.R. Bhisetti, U.S. Patent 5,558,397 (1996). The scheme shown here is partly based on that used to prepare darunavir and fosamprenavir due to difficulty in deciphering the patent.
See also
- Fosamprenavir, a prodrug of amprenavir
External links
- Amprenavir bound to proteins in the PDB
- ^ Shen, C. H.; Wang, Y. F.; Kovalevsky, A. Y.; Harrison, R. W.; Weber, I. T. (2010). "Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters". FEBS Journal 277 (18): 3699–3714. doi:10.1111/j.1742-4658.2010.07771.x. PMC 2975871. PMID 20695887. edit
- ^ Getman, D. P.; Decrescenzo, G. A.; Heintz, R. M.; Reed, K. L.; Talley, J. J.; Bryant, M. L.; Clare, M.; Houseman, K. A.; Marr, J. J. (1993). "Discovery of a novel class of potent HIV-1 protease inhibitors containing the (R)-(hydroxyethyl)urea isostere". Journal of Medicinal Chemistry 36 (2): 288. doi:10.1021/jm00054a014. edit
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Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)
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Entry/fusion inhibitors
(Discovery and development) |
- gp41 (Enfuvirtide (ENF, T-20))
- CCR5 (Maraviroc (MVC)
- Vicriviroc†, Cenicriviroc†, PRO 140†)
- CD4 (Ibalizumab†)
- gp120 (Fostemsavir†)
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Reverse-transcriptase
inhibitors (RTIs) |
Nucleoside and
nucleotide (NRTI) |
- Nucleoside analogues/NARTIs: Abacavir (ABC)°#
- Emtricitabine (FTC)°#
- Lamivudine (3TC)°#
- Didanosine (ddI)#
- Zidovudine (AZT, ZDV)#
- Apricitabine†
- Stampidine†
- Elvucitabine†
- Racivir†
- Amdoxovir†
- Stavudine (d4T)#
- Zalcitabine (ddC)◊
- Festinavir†
- Nucleotide analogues/NtRTIs: Tenofovir disoproxil fumarate (TDF)°#
- Tenofovir alafenamide fumarate (TAF)†
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Non-nucleoside (NNRTI)
(Discovery and development) |
- (1st generation) Efavirenz (EFV)°#
- Nevirapine (NVP)#
- Delavirdine (DLV)◊
(2nd generation) diarylpyrimidines (Etravirine (ETR)- Rilpivirine (RPV)°)
- Doravirine
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| Integrase inhibitors |
- Raltegravir (RAL)°
- Elvitegravir (EVG)°
- Dolutegravir (DTG)°
- Globoidnan A (experimental)
- MK-2048†
- BI 224436†
- Cabotegravir†
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| Maturation inhibitors |
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Protease Inhibitors (PI)
(Discovery and development) |
| 1st generation |
- Fosamprenavir (FPV)
- Lopinavir (LPV)°#
- Nelfinavir (NFV)#
- Ritonavir (RTV)#
- Saquinavir (SQV)#
- Amprenavir (APV)◊
- Indinavir (IDV)◊#
- Telinavir
- Droxinavir
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| 2nd generation |
- Atazanavir (ATV)°
- Darunavir (DRV)°
- Tipranavir (TPV)
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| Combined formulations |
- Abacavir/lamivudine°
- Abacavir/dolutegravir/lamivudine°
- Abacavir/lamivudine/zidovudine
- Atazanavir/cobicistat
- Darunavir/cobicistat
- Efavirenz/emtricitabine/tenofovir°
- Elvitegravir/cobicistat/emtricitabine/tenofovir°
- Emtricitabine/rilpivirine/tenofovir°
- Lamivudine/raltegravir
- Lamivudine/zidovudine
- Lopinavir/ritonavir°
- Tenofovir/emtricitabine°
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| Pharmacokinetic boosters |
- Ritonavir (r)
- Cobicistat (c)
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| Experimental agents |
| Uncoating inhibitors |
|
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| Transcription inhibitors |
|
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| Translation inhibitors |
|
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| Other |
- Abzyme
- Calanolide A
- Ceragenin
- Cyanovirin-N
- Diarylpyrimidines
- Epigallocatechin gallate (EGCG)
- Foscarnet
- Griffithsin
- Hydroxycarbamide
- Miltefosine
- Portmanteau inhibitors
- Scytovirin
- Seliciclib†
- Synergistic enhancers
- Tre recombinase
- Zinc finger protein transcription factor
- KP-1461†
- BIT225†
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| Failed agents |
- Aplaviroc
- Atevirdine
- Brecanavir
- Capravirine
- Dexelvucitabine
- Emivirine
- Lersivirine
- Lodenosine
- Loviride
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
°DHHS recommended initial regimen options. ◊Formerly or rarely used agent.
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Index of viral disease
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| Description |
|
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| Disease |
- Systemic
- Cutaneous
- Zoster
- Human papillomavirus
- Zoonotic
- Symptoms and signs
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| Treatment |
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UpToDate Contents
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English Journal
- Structural and Thermodynamic Basis of Amprenavir/Darunavir and Atazanavir Resistance in HIV-1 Protease with Mutations at Residue 50.
- Mittal S, Bandaranayake RM, King NM, Prabu-Jeyabalan M, Nalam MN, Nalivaika EA, Kurt Yilmaz N, Schiffer CA.SourceDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- Journal of virology.J Virol.2013 Apr;87(8):4176-84. doi: 10.1128/JVI.03486-12. Epub 2013 Jan 30.
- Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the
- PMID 23365446
- Discordant Associations Between SLCO1B1 521T→C and Plasma Levels of Ritonavir-boosted Protease Inhibitors in AIDS Clinical Trials Group Study A5146.
- Zhang X, Tierney C, Albrecht M, Demeter LM, Morse G, Difrancesco R, Dykes C, Jiang H, Haas DW.Source*Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts †Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts ‡School of Medicine and Dentistry, University of Rochester, Rochester, New York §Department of Pharmacy Practice, Translational Pharmacology Research Core, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York ¶Harvard Medical School ‖Departments of Medicine, Pharmacology, Pathology, Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, Tennessee.
- Therapeutic drug monitoring.Ther Drug Monit.2013 Apr;35(2):209-216.
- OBJECTIVE:: Among HIV-positive patients prescribed ritonavir-boosted lopinavir, SLCO1B1 521T→C (rs4149056) is associated with increased plasma lopinavir exposure. Protease inhibitors (PIs) are also substrates for cytochrome P450 (CYP) 3A and ABCB1, which are induced by NR1I2. We characterized rela
- PMID 23503447
- Pregnane X Receptor Mediates Dyslipidemia Induced by the HIV Protease Inhibitor Amprenavir in Mice.
- Helsley RN, Sui Y, Ai N, Park SH, Welsh WJ, Zhou C.Source1 University of Kentucky;
- Molecular pharmacology.Mol Pharmacol.2013 Mar 21. [Epub ahead of print]
- HIV protease inhibitors (PIs) have been used successfully in extending the lifespan of people infected with HIV. The use of PIs has also been associated with dyslipidemia and an increased risk of cardiovascular disease but the underlying mechanisms remain elusive. Several PIs have been implicated to
- PMID 23519392
Japanese Journal
- HIVプロテアーゼ阻害薬アンプレナビル(プローゼ^<【○!R】>力プセル)の薬理学的特性と臨床効果
- 石澤 優,小松 英忠
- 日本薬理学雑誌 117(1), 59-64, 2001-01-01
- アンプレナビル(プローゼ<SUP>®</SUP>カプセル)は, HIVプロテアーゼ阻害薬で米国の臨床試験においてその有効性が証明され, 1999年に承認された.本邦においても同年9月に承認されている(キッセイ薬品工業株式会社より10月に発売).本剤は, 通常成人にはアンプレナビルとして1回1200mg(8カプセル)を1日2回, 他の抗HIV薬との併用により経口投与される. …
- NAID 10007943025
Related Links
- Learn about the prescription medication Agenerase Capsules (Amprenavir Capsules), drug uses, dosage, side effects, drug interactions, warnings, reviews and patient labeling. ... Amprenavir is a white to cream-colored solid with a ...
- Agenerase official prescribing information for healthcare professionals. Includes: indications, dosage, adverse reactions, pharmacology and more. ... The relative bioavailability of Agenerase Capsules and Oral Solution was assessed ...
Related Pictures
★リンクテーブル★
[★]
- 英
- amprenavir APV
- 商
- レクシヴァ、プローゼ、Agenerase