Amprenavir

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Amprenavir
Amprenavir structure.svg
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
Pregnancy
category
  • US: C (Risk not ruled out)
Legal status
  • (Prescription only)
Routes of
administration
Oral (capsules)
Pharmacokinetic data
Protein binding 90%
Metabolism hepatic
Biological half-life 7.1-10.6 hours
Excretion <3% renal
Identifiers
CAS Number 161814-49-9 YesY
ATC code J05AE05
PubChem CID 65016
DrugBank DB00701 YesY
ChemSpider 58532 YesY
UNII 5S0W860XNR YesY
KEGG D00894 YesY
ChEBI CHEBI:40050 YesY
ChEMBL CHEMBL116 YesY
NIAID ChemDB 006080
Chemical data
Formula C25H35N3O6S
Molar mass 505.628 g/mol
  (verify)

Amprenavir (original brand name 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 1.2 mg, delivered in 8 (eight) very large 150 mg gel capsules or 24 (twenty-four) 50 mg gel capsules twice daily.[1]

Production of amprenavir was discontinued by the manufacturer on December 31, 2004; a prodrug version (fosamprenavir, brand name Telzir/Lexiva) is available.

HIV-1 Protease dimer with Amprenavir (sticks) bound in the active site. PDB entry 3nu3 [2]

Background[edit]

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[edit]

[3]

Roger D. Tung, Mark A. Murcko, Govinda R. Bhisetti, U.S. Patent 7,608,632 (1994). The scheme shown here is partly based on that used to prepare darunavir and fosamprenavir due to difficulty in deciphering the patent.

See also[edit]

  • Fosamprenavir, a prodrug of amprenavir with improved pharmacokinetic parameters and dosing regimen

External links[edit]


  1. ^ "Agenerase (amprenavir) Capsules. Full Prescribing Information. Section Dosage and Administration" (PDF). US Food and Drug Administration (http://www.fda.gov). GlaxoSmithKline and Vertex Pharmaceuticals Inc. Retrieved 29 November 2015. 
  2. ^ 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. 
  3. ^ 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.