Delavirdine

Delavirdine
Clinical data
Trade names Rescriptor
AHFS/Drugs.com Monograph
MedlinePlus a600034
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration		 Oral
ATC code J05AG02 (WHO)
Legal status
Legal status
Pharmacokinetic data
Bioavailability 85%
Protein binding 98%
Metabolism Hepatic (CYP3A4- and CYP2D6-mediated)
Biological half-life 5.8 hours
Excretion Renal (51%) and fecal (44%)
Identifiers
CAS Number 136817-59-9 YesY
PubChem (CID) 5625
DrugBank DB00705 YesY
ChemSpider 5423 YesY
UNII DOL5F9JD3E YesY
KEGG D07782 YesY
ChEBI CHEBI:119573 YesY
ChEMBL CHEMBL593 YesY
NIAID ChemDB 005059
Chemical and physical data
Formula C22H28N6O3S
Molar mass 456.562 g/mol
3D model (Jmol) Interactive image
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Delavirdine (DLV) (brand name Rescriptor) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) marketed by ViiV Healthcare. It is used as part of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) type 1. It is presented as the mesylate. The recommended dosage is 400 mg, three times a day.

Although delavirdine was approved by the U.S. Food and Drug Administration in 1997, its efficacy is lower than other NNRTIs, especially efavirenz, and it also has an inconvenient schedule. These factors have led the U.S. DHHS not to recommend its use as part of initial therapy.[1] The risk of cross-resistance across the NNRTI class, as well as its complex set of drug interactions, make the place of delavirdine in second-line and salvage therapy unclear, and it is currently rarely used.

Interactions

Like ritonavir, delavirdine is an inhibitor of cytochrome P450 isozyme CYP3A4, and interacts with many medications. It should not be administered with a wide range of drugs, including amprenavir, fosamprenavir, simvastatin, lovastatin, rifampin, rifabutin, rifapentine, St John's wort, astemizole, midazolam, triazolam, ergot medications, and several medications for acid reflux.[1]

Adverse effects

The most common adverse event is moderate to severe rash, which occurs in up to 20% of patients.[2] Other common adverse events include fatigue, headache and nausea. Liver toxicity has also been reported.

Synthesis

Delavirdine synthesis:[3][4]

Modification of the scheme that was done for ateviridine q.v. by performing the reductive alkylation with acetone gives 2 after removal of the protecting group. Acylation of this amine with the imidazolide from 5-Methylsulfonaminoindole-2-carboxylic acid (1) affords the amide, reverse transcriptase inhibitor, atevirdine.

References

  1. 1 2 DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from AIDSInfo)
  2. ↑ RESCRIPTOR brand of delavirdine mesylate tablets. Product information.
  3. ↑ D. L. Romero et al., WO 9109849; J. R. Palmer et al., U.S. Patent 5,563,142 (1991, 1996 both to Upjohn).
  4. ↑ Romero, D. L.; Morge, R. A.; Genin, M. J.; Biles, C.; Busso, M.; Resnick, L.; Althaus, I. W.; Reusser, F.; Thomas, R. C.; Tarpley, W. G. (1993). "Bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: Structure-activity relationships of novel substituted indole analogs and the identification of 1-[(5-methanesulfonamido-1H-indol-2-yl)carbonyl]-4-[3-[(1-methylethyl)amino]pyridinyl]piperazinemonomethanesulfonate (U-90152S), a second-generation clinical candidate". Journal of Medicinal Chemistry. 36 (10): 1505. doi:10.1021/jm00062a027. PMID 7684450.
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