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.
Its manufacturing and distribution was discontinued in the United States and Canada.[2][3][4]
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.
Modification of the scheme that was done for ateviridineq.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
^ abDHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from AIDSInfo 2006-05-06 at the Wayback Machine)
^RPh, Diana Ernst (11 May 2017). "HIV Drug Soon to Be Unavailable". MPR.
^"Delavirdine: Indications, Side Effects, Warnings". Drugs.com.
^"Prescription drug RESCRIPTOR (delavirdine mesylate) – DrugFinder.ca". drugfinder.ca.
^(PDF). Archived from the original (PDF) on 2006-04-15. Retrieved 2006-05-18.
^WO 9109849, Romero DL, Mitchell MA, Thomas RC, Palmer JR, Tarpley WG, Aristoff PA, Smith HW, "Diaromatic Substituted Anti-AIDS Compounds", published 11 July 1991, assigned to Upjohn Company
^US 5563142, Palmer JR, Romero DL, Aristoff PA, Thomas RC, Smith HW, "Diaromatic substituted compounds as anti-HIV-1 agents", published 8 October 1996, assigned to Upjohn Company
^Romero DL, Morge RA, Genin MJ, Biles C, Busso M, Resnick L, et al. (May 1993). "Bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: structure-activity relationships of novel substituted indole analogues and the identification of 1-[(5-methanesulfonamido-1H-indol-2-yl)-carbonyl]-4-[3- [(1-methylethyl)amino]-pyridinyl]piperazine monomethanesulfonate (U-90152S), a second-generation clinical candidate". Journal of Medicinal Chemistry. 36 (10): 1505–8. doi:10.1021/jm00062a027. PMID 7684450.
External links
"Delavirdine". Drug Information Portal. U.S. National Library of Medicine.
delavirdine, brand, name, rescriptor, nucleoside, reverse, transcriptase, inhibitor, nnrti, marketed, viiv, healthcare, used, part, highly, active, antiretroviral, therapy, haart, treatment, human, immunodeficiency, virus, type, presented, mesylate, recommende. 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 DelavirdineClinical dataTrade namesRescriptorAHFS Drugs comMonographMedlinePlusa600034PregnancycategoryAU B3Routes ofadministrationBy mouthATC codeJ05AG02 WHO Legal statusLegal statusUS onlyPharmacokinetic dataBioavailability85 Protein binding98 MetabolismLiver CYP3A4 and CYP2D6 mediated Elimination half life5 8 hoursExcretionKidney 51 and feces 44 IdentifiersIUPAC name N 2 4 3 propan 2 ylamino pyridin 2 yl piperazin 1 yl carbonyl 1H indol 5 yl methanesulfonamideCAS Number136817 59 9 YPubChem CID5625DrugBankDB00705 YChemSpider5423 YUNIIDOL5F9JD3EKEGGD07782 YChEBICHEBI 119573 YChEMBLChEMBL593 YNIAID ChemDB005059PDB ligandSPP PDBe RCSB PDB CompTox Dashboard EPA DTXSID6022892Chemical and physical dataFormulaC 22H 28N 6O 3SMolar mass456 57 g mol 13D model JSmol Interactive imageSMILES CC C Nc1cccnc1N4CCN C O c3cc2cc NS C O O ccc2 nH 3 CC4InChI 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 YKey WHBIGIKBNXZKFE UHFFFAOYSA N Y verify 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 Its manufacturing and distribution was discontinued in the United States and Canada 2 3 4 Contents 1 Interactions 2 Adverse effects 3 Synthesis 4 References 5 External linksInteractions EditLike 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 EditThe 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 Edit 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 References Edit a b DHHS panel Guidelines for the use of antiretroviral agents in HIV 1 infected adults and adolescents May 4 2006 Available for download from AIDSInfo Archived 2006 05 06 at the Wayback Machine RPh Diana Ernst 11 May 2017 HIV Drug Soon to Be Unavailable MPR Delavirdine Indications Side Effects Warnings Drugs com Prescription drug RESCRIPTOR delavirdine mesylate DrugFinder ca drugfinder ca RESCRIPTOR brand of delavirdine mesylate tablets Product information PDF Archived from the original PDF on 2006 04 15 Retrieved 2006 05 18 WO 9109849 Romero DL Mitchell MA Thomas RC Palmer JR Tarpley WG Aristoff PA Smith HW Diaromatic Substituted Anti AIDS Compounds published 11 July 1991 assigned to Upjohn Company US 5563142 Palmer JR Romero DL Aristoff PA Thomas RC Smith HW Diaromatic substituted compounds as anti HIV 1 agents published 8 October 1996 assigned to Upjohn Company Romero DL Morge RA Genin MJ Biles C Busso M Resnick L et al May 1993 Bis heteroaryl piperazine BHAP reverse transcriptase inhibitors structure activity relationships of novel substituted indole analogues and the identification of 1 5 methanesulfonamido 1H indol 2 yl carbonyl 4 3 1 methylethyl amino pyridinyl piperazine monomethanesulfonate U 90152S a second generation clinical candidate Journal of Medicinal Chemistry 36 10 1505 8 doi 10 1021 jm00062a027 PMID 7684450 External links Edit Delavirdine Drug Information Portal U S National Library of Medicine Portals Medicine Viruses Retrieved from https en wikipedia org w index php title Delavirdine amp oldid 1131068130, wikipedia, wiki, book, books, library,
