Darunavir

Title: Darunavir
CAS Registry Number: 206361-99-1
CAS Name: [(1S,2R)-3-[[(4-Aminophenyl)sulfonyl] (2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester
Additional Names: (1S,2R,3¢R,3¢aS,6¢aR)-[3¢-hexahydrofuro[2,3-b]furanyl-[3-(4-aminobenzenesulfonyl)isobutylamino]-1-benzyl-2-hydroxypropyl]carbamate
Manufacturers' Codes: TMC-114; UIC-94017
Molecular Formula: C27H37N3O7S
Molecular Weight: 547.66
Percent Composition: C 59.21%, H 6.81%, N 7.67%, O 20.45%, S 5.85%
Literature References: Second generation HIV-1 protease inhibitor; structurally similar to amprenavir, q.v. Prepn: A. K. Ghosh et al., Bioorg. Med. Chem. Lett. 8, 687 (1998); idem et al., J. Org. Chem. 69, 7822 (2004). See also: J. W. Erickson, S. V. Gulnik, WO 9967417 (1999 to U.S. Dept. Health Human Serv.); J. W. Erickson et al., US 05158713 (2005 to Univ. Illinois). In vitro activity vs multidrug resistant HIV isolates: Y. Koh et al., Antimicrob. Agents Chemother. 47, 3123 (2003). Crystal structures of complex with protease variants: Y. Tie et al., J. Mol. Biol. 338, 341 (2004). Structure activity study and pharmacokinetic analysis: D. L. N. G. Surleraux et al., J. Med. Chem. 48, 1813 (2005). Review of pharmacology and clinical experience: A. C. Shurtleff, Curr. Opin. Invest. Drugs 5, 879-886 (2004). Clinical evaluation of combination with ritonavir: K. Arastéh et al., AIDS 19, 943 (2005).
Properties: White amorphous solid, mp 74° (dec).
Melting point: mp 74° (dec)
Therap-Cat: Antiviral.
Keywords: Antiviral; Peptidomimetics; HIV Protease Inhibitor.
Darvan? Dasatinib Datiscetin Daucol Daunorubicin

Darunavir
Darunavir.svg
Darunavir ball-and-stick animation.gif
Systematic (IUPAC) name
[(1R,5S,6R)-2,8-dioxabicyclo[3.3.0]oct-6-yl] N-[(2S,3R)-4- [(4-aminophenyl)sulfonyl- (2-methylpropyl)amino]-3-hydroxy-1-phenyl- butan-2-yl] carbamate
Clinical data
Trade names Prezista
AHFS/Drugs.com monograph
MedlinePlus a607042
Pregnancy cat. B
Legal status  ?
Routes oral
Pharmacokinetic data
Protein binding 95%
Metabolism hepatic (CYP)
Half-life 15 hours
Identifiers
CAS number 206361-99-1 YesY
ATC code J05AE10
PubChem CID 213039
DrugBank DB01264
ChemSpider 184733 YesY
UNII YO603Y8113 YesY
KEGG D03656 YesY
ChEBI CHEBI:367163 YesY
ChEMBL CHEMBL1323 N
NIAID ChemDB 073035
Chemical data
Formula C27H37N3O7S 
Mol. mass 547.665 g/mol
 N (what is this?)  (verify)

Darunavir (brand name Prezista, formerly known as TMC114) is a protease inhibitor drug used to treat HIV infection. Prezista is an OARAC recommended treatment option for treatment-naïve and treatment-experienced adults and adolescents.[1] Developed by pharmaceutical company Tibotec, darunavir is named after Arun K. Ghosh, the chemist who discovered the molecule at the University of Illinois at Chicago. It was approved by the Food and Drug Administration (FDA) on June 23, 2006.[2]

Darunavir is a second-generation protease inhibitor (PIs), designed specifically to overcome problems with the older agents in this class, such as indinavir. Early PIs often have severe side effects and drug toxicities, require a high therapeutic dose, are costly to manufacture, and show a disturbing susceptibility to drug resistant mutations. Such mutations can develop in as little as a year of use, and effectively render the drugs useless.

Darunavir was designed to form robust interactions with the protease enzyme from many strains of HIV, including strains from treatment-experienced patients with multiple resistance mutations to PIs.[3][4]

Darunavir received much attention at the time of its release, as it represents an important treatment option for patients with drug-resistant HIV. Patient advocacy groups pressured developer Tibotec not to follow the previous trend of releasing new drugs at prices higher than existing drugs in the same class. Darunavir was priced to match other common PIs already in use, such as the fixed-dose combination drug lopinavir/ritonavir.