Amprenavir

Amprenavir

File: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 Y
ATC code	J05AE05 (WHO)
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
Molecular mass	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
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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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.

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

File:3nu3 478.png

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

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

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

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

External links

• Amprenavir bound to proteins in the PDB