Delavirdine

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.

Delavirdine

Clinical data
Trade names	Rescriptor
AHFS/Drugs.com	Monograph
MedlinePlus	a600034
Pregnancy category	AU: B3
Routes of administration	By mouth
ATC code	J05AG02 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	85%
Protein binding	98%
Metabolism	Liver (CYP3A4- and CYP2D6-mediated)
Elimination half-life	5.8 hours
Excretion	Kidney (51%) and feces (44%)
Identifiers
IUPAC name N-[2-({4-[3-(propan-2-ylamino)pyridin-2-yl]piperazin-1-yl}carbonyl)-1H-indol-5-yl]methanesulfonamide
CAS Number	136817-59-9 Y
PubChem CID	5625
DrugBank	DB00705 Y
ChemSpider	5423 Y
UNII	DOL5F9JD3E
KEGG	D07782 Y
ChEBI	CHEBI:119573 Y
ChEMBL	ChEMBL593 Y
NIAID ChemDB	005059
PDB ligand	SPP (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID6022892
Chemical and physical data
Formula	C22H28N6O3S
Molar mass	456.57 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)Nc1cccnc1N4CCN(C(=O)c3cc2cc(NS(C)(=O)=O)ccc2[nH]3)CC4
InChI InChI=1S/C22H28N6O3S/c1-15(2)24-19-5-4-8-23-21(19)27-9-11-28(12-10-27)22(29)20-14-16-13-17(26-32(3,30)31)6-7-18(16)25-20/h4-8,13-15,24-26H,9-12H2,1-3H3 Y Key:WHBIGIKBNXZKFE-UHFFFAOYSA-N Y
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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, makes the place of delavirdine in second-line and salvage therapy unclear, and it is currently rarely used.

Its manufacturing and distribution was discontinued in the United States and Canada.^[2][3][4]

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, 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.^[5] Other common adverse events include fatigue, headache and nausea. Liver toxicity has also been reported.

Synthesis

Delavirdine synthesis:^[6][7][8]

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.