Thursday 3 July 2014

Amprenavir (Agenerase, GlaxoSmithKline) is a protease inhibitor.......

Amprenavir skeletal.svg
AMPRENAVIR

Amprenavir (AgeneraseGlaxoSmithKline) 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]


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 namesAgenerase
AHFS/Drugs.commonograph
MedlinePlusa699051
Licence dataEMA:LinkUS FDA:link
Pregnancy cat.(US)
  
Routesoral
Pharmacokinetic data
Protein binding90%
Metabolismhepatic
Half-life7.1-10.6 hours
Excretion<3% renal
Identifiers
CAS number161814-49-9 Yes
ATC codeJ05AE05
PubChemCID 65016
DrugBankDB00701
ChemSpider58532 Yes
UNII5S0W860XNR Yes
KEGGD00894 Yes
ChEBICHEBI:40050 Yes
ChEMBLCHEMBL116 Yes
NIAID ChemDB006080
Chemical data
FormulaC25H35N3O6S 
Mol. mass505.628 g/mol
 
 
 
Amprenavir (AgeneraseGlaxoSmithKline) 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
......................

New approaches to the industrial synthesis of HIV protease inhibitors


http://pubs.rsc.org/en/content/articlelanding/2004/ob/b404071f/unauth#!divAbstract
Efficient and industrially applicable synthetic processes for precursors of HIV protease inhibitors (Amprenavir, Fosamprenavir) are described. These involve a novel and economical method for the preparation of a key intermediate, (3S)-hydroxytetrahydrofuran, from L-malic acid. Three new approaches to the assembly of Amprenavir are also discussed. Of these, a synthetic route in which an (S)-tetrahydrofuranyloxy carbonyl is attached to L-phenylalanine appears to be the most promising manufacturing process, in that it offers satisfactory stereoselectivity in fewer steps.
Graphical abstract: New approaches to the industrial synthesis of HIV protease inhibitors
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AGENERASE (amprenavir) is an inhibitor of the human immunodeficiency virus (HIVprotease. The chemical name of amprenavir is (3S)-tetrahydro-3-furyl N-[(1S,2R)-3-(4-amino-N-isobutylbenzenesulfonamido)-1-benzyl-2-hydroxypropyl]carbamate. Amprenavir is a single stereoisomer with the (3S)(1S,2R) configuration. It has a molecular formula of C25H35N3O6S and a molecular weight of 505.64. It has the following structural formula:

AGENERASE® (amprenavir)  Structural Formula Illustration

Amprenavir is a white to cream-colored solid with a solubility of approximately 0.04 mg/mL in water at 25°C.
AGENERASE Capsules (amprenavir capsules) are
available for oral administration. Each 50- mg capsule contains the inactive ingredients d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), polyethylene glycol 400 (PEG 400) 246.7 mg, and propylene glycol 19 mg. The capsule shell contains the inactive ingredients d-sorbitol and sorbitans solution, gelatin, glycerin, and titanium dioxide. The soft gelatin capsules are printed with edible red ink. Each 50- mg AGENERASE Capsule contains 36.3 IU vitamin E in the form of TPGS. The total amount of vitamin E in the recommended daily adult dose of AGENERASE is 1,744 IU.


See also

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