Delavirdine

Identification

Summary

Delavirdine is a non-nucleoside reverse transcriptase inhibitor used to treat HIV infection.

Generic Name
Delavirdine
DrugBank Accession Number
DB00705
Background

A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 456.561
Monoisotopic: 456.194359482
Chemical Formula
C22H28N6O3S
Synonyms
  • (N-[2-[4-[3-(1-methylethylamino)pyridin-2-yl]piperazin-1-yl]carbonyl-1H-indol-5-yl] methanesulfonamide)
  • 1-(3-((1-methylethyl)amino)-2-pyridinyl)-4-((5-((methylsulfonyl)amino)-1H-indol-2-yl)carbonyl)piperazine
  • 2-(4-(5-methanesulfonamido-1H-indol-2-ylcarbonyl)-1-piperazinyl)-N-(1-methylethyl)-3-pyridinamine
  • Delavirdin
  • Delavirdina
  • Delavirdine
  • Delavirdinum
  • N-(2-(1-(3-(isopropylamino)pyridin-2-yl)piperazine-4-carbonyl)-1H-indol-5-yl)methanesulfonamide
  • N-{2-[4-(3-Isopropylamino-pyridin-2-yl)-piperazine-1-carbonyl]-1H-indol-5-yl}-methanesulfonamide
External IDs
  • U 90152 S

Pharmacology

Indication

For the treatment of HIV-1 infection in combination with appropriate antiretroviral agents when therapy is warranted

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatHiv-1 infection••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Delavirdine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Delavirdine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of Delavirdine does not compete with template or nucleoside triphosphates. HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by Delavirdine.

Mechanism of action

Delavirdine binds directly to viral reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by disrupting the enzyme's catalytic site.

TargetActionsOrganism
AReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
Absorption

Rapidly absorbed

Volume of distribution

Not Available

Protein binding

98%

Metabolism

Hepatic

Hover over products below to view reaction partners

Route of elimination

Delavirdine is extensively converted to several inactive metabolites by cytochrome P450 3A (CYP3A). Delavirdine was excreted in the milk of lactating rats at a concentration three to five times that of rat plasma.

Half-life

5.8 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Major toxicity of delavirdine is rash and should be advised to promptly notify their physician should rash occur. The majority of rashes associated with delavirdine occur within 1 to 3 weeks after initiating treatment with delavirdine. The rash normally resolves in 3 to 14 days and may be treated symptomatically while therapy with delavirdine is continued. Any patient experiencing severe rash or rash accompanied by symptoms such as fever, blistering, oral lesions, conjunctivitis, swelling, muscle or joint aches should discontinue medication and consult a physician.

Pathways
PathwayCategory
Delavirdine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Delavirdine.
AbametapirThe serum concentration of Delavirdine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Delavirdine can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Delavirdine.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Delavirdine.
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Delavirdine mesylate421105KRQE147221-93-0MEPNHSOMXMALDZ-UHFFFAOYSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RescriptorTablet200 mg/1OralViiV Healthcare Company2010-10-132010-10-13US flag
RescriptorTablet100 mg/1OralAgouron Pharmaceuticals1997-04-182011-04-30US flag
RescriptorTablet200 mg/1OralViiV Healthcare Company2012-04-112020-08-31US flag
RescriptorTablet200 mg/1OralKaiser Foundations Hospitals2011-07-062013-06-30US flag
RescriptorTablet100 mgOralViiV Healthcare ULC1998-07-242018-11-01Canada flag

Categories

ATC Codes
J05AG02 — Delavirdine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyridinylpiperazines. These are compounds containing a pyridinylpiperazine skeleton, which consists of a pyridine linked (not fused) to a piperazine by a bond by a single bond that is not part of a ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Pyridinylpiperazines
Alternative Parents
Indolecarboxamides and derivatives / N-arylpiperazines / Sulfanilides / Indoles / 2-heteroaryl carboxamides / Dialkylarylamines / Pyrrole carboxamides / Secondary alkylarylamines / Aminopyridines and derivatives / Organic sulfonamides
show 12 more
Substituents
2-heteroaryl carboxamide / Amine / Amino acid or derivatives / Aminopyridine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carboxamide group / Carboxylic acid derivative
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfonamide, N-carbonylpiperazine, aminopyridine, indolecarboxamide (CHEBI:119573)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
DOL5F9JD3E
CAS number
136817-59-9
InChI Key
WHBIGIKBNXZKFE-UHFFFAOYSA-N
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
IUPAC Name
N-[2-(4-{3-[(propan-2-yl)amino]pyridin-2-yl}piperazine-1-carbonyl)-1H-indol-5-yl]methanesulfonamide
SMILES
CC(C)NC1=C(N=CC=C1)N1CCN(CC1)C(=O)C1=CC2=C(N1)C=CC(NS(C)(=O)=O)=C2

References

Synthesis Reference
US5563142
General References
Not Available
Human Metabolome Database
HMDB0014843
KEGG Compound
C06941
PubChem Compound
5625
PubChem Substance
46508878
ChemSpider
5423
BindingDB
1944
RxNav
83816
ChEBI
119573
ChEMBL
CHEMBL593
ZINC
ZINC000018516586
Therapeutic Targets Database
DAP000183
PharmGKB
PA449223
PDBe Ligand
SPP
Drugs.com
Drugs.com Drug Page
Wikipedia
Delavirdine
PDB Entries
1klm
FDA label
Download (645 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Viiv healthcare co
Packagers
  • Agouron Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Kaiser Foundation Hospital
  • Pfizer Inc.
  • Pharmacia Inc.
  • Physicians Total Care Inc.
  • ViiV Healthcare ULC
Dosage Forms
FormRouteStrength
TabletOral100 mg
TabletOral100 mg/1
TabletOral200 mg/1
Prices
Unit descriptionCostUnit
Rescriptor 200 mg tablet1.92USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5563142No1996-10-082013-10-08US flag
CA2184598No2005-05-032015-03-01Canada flag
CA2071529No2001-03-202010-12-24Canada flag
US6177101No2001-01-232019-06-07US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)226-228 °CNot Available
logP2.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.086 mg/mLALOGPS
logP2.77ALOGPS
logP1.02Chemaxon
logS-3.7ALOGPS
pKa (Strongest Acidic)9.39Chemaxon
pKa (Strongest Basic)6.82Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area110.43 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity126.64 m3·mol-1Chemaxon
Polarizability49.99 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier-0.6449
Caco-2 permeable-0.6231
P-glycoprotein substrateSubstrate0.7103
P-glycoprotein inhibitor IInhibitor0.7647
P-glycoprotein inhibitor IINon-inhibitor0.5644
Renal organic cation transporterNon-inhibitor0.7808
CYP450 2C9 substrateNon-substrate0.6717
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.6707
CYP450 1A2 substrateNon-inhibitor0.6644
CYP450 2C9 inhibitorInhibitor0.6307
CYP450 2D6 inhibitorNon-inhibitor0.8556
CYP450 2C19 inhibitorNon-inhibitor0.6078
CYP450 3A4 inhibitorNon-inhibitor0.6383
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9308
Ames testNon AMES toxic0.6189
CarcinogenicityNon-carcinogens0.7517
BiodegradationNot ready biodegradable0.9891
Rat acute toxicity2.5840 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7656
hERG inhibition (predictor II)Inhibitor0.6118
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-004i-1869800000-919b00dc1b3b74381f73
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0000900000-81c4c2deddb329078e0b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0000900000-6c547a7479f895edc33f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0004900000-055907f9c46e7c0ec1ed
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0114900000-d38593a50e2ca8579a67
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0bu0-0119100000-88e641df8f022d8c7e5f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-08iu-1933500000-832a021dc9c1372d08a8
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-233.6803003
predicted
DarkChem Lite v0.1.0
[M-H]-238.1674003
predicted
DarkChem Lite v0.1.0
[M-H]-238.4311003
predicted
DarkChem Lite v0.1.0
[M-H]-198.25618
predicted
DeepCCS 1.0 (2019)
[M+H]+233.6717003
predicted
DarkChem Lite v0.1.0
[M+H]+238.4894003
predicted
DarkChem Lite v0.1.0
[M+H]+238.2737003
predicted
DarkChem Lite v0.1.0
[M+H]+200.65175
predicted
DeepCCS 1.0 (2019)
[M+Na]+233.7769003
predicted
DarkChem Lite v0.1.0
[M+Na]+238.7264003
predicted
DarkChem Lite v0.1.0
[M+Na]+239.1959003
predicted
DarkChem Lite v0.1.0
[M+Na]+206.56427
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72547
Uniprot Name
Reverse transcriptase/RNaseH
Molecular Weight
65223.615 Da
References
  1. Geitmann M, Unge T, Danielson UH: Biosensor-based kinetic characterization of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors. J Med Chem. 2006 Apr 20;49(8):2367-74. [Article]
  2. Xia Q, Radzio J, Anderson KS, Sluis-Cremer N: Probing nonnucleoside inhibitor-induced active-site distortion in HIV-1 reverse transcriptase by transient kinetic analyses. Protein Sci. 2007 Aug;16(8):1728-37. [Article]
  3. Freimuth WW: Delavirdine mesylate, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor. Adv Exp Med Biol. 1996;394:279-89. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Voorman RL, Maio SM, Payne NA, Zhao Z, Koeplinger KA, Wang X: Microsomal metabolism of delavirdine: evidence for mechanism-based inactivation of human cytochrome P450 3A. J Pharmacol Exp Ther. 1998 Oct;287(1):381-8. [Article]
  3. von Moltke LL, Greenblatt DJ, Granda BW, Giancarlo GM, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. J Clin Pharmacol. 2001 Jan;41(1):85-91. doi: 10.1177/00912700122009728. [Article]
  4. Tran JQ, Gerber JG, Kerr BM: Delavirdine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2001;40(3):207-26. doi: 10.2165/00003088-200140030-00005. [Article]
  5. Fichtenbaum CJ, Gerber JG: Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. Clin Pharmacokinet. 2002;41(14):1195-211. doi: 10.2165/00003088-200241140-00004. [Article]
  6. Shelton MJ, Hewitt RG, Adams J, Della-Coletta A, Cox S, Morse GD: Pharmacokinetics of ritonavir and delavirdine in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2003 May;47(5):1694-9. doi: 10.1128/aac.47.5.1694-1699.2003. [Article]
  7. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L54). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
  8. Flockhart Table of Drug Interactions [Link]
  9. Delavirdine FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Voorman RL, Payne NA, Wienkers LC, Hauer MJ, Sanders PE: Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6. Drug Metab Dispos. 2001 Jan;29(1):41-7. [Article]
  2. Voorman RL, Maio SM, Hauer MJ, Sanders PE, Payne NA, Ackland MJ: Metabolism of delavirdine, a human immunodeficiency virus type-1 reverse transcriptase inhibitor, by microsomal cytochrome P450 in humans, rats, and other species: probable involvement of CYP2D6 and CYP3A. Drug Metab Dispos. 1998 Jul;26(7):631-9. [Article]
  3. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L54). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. von Moltke LL, Greenblatt DJ, Granda BW, Giancarlo GM, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. J Clin Pharmacol. 2001 Jan;41(1):85-91. doi: 10.1177/00912700122009728. [Article]
  2. Voorman RL, Payne NA, Wienkers LC, Hauer MJ, Sanders PE: Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6. Drug Metab Dispos. 2001 Jan;29(1):41-7. [Article]
  3. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L54). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
  4. Delavirdine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Voorman RL, Payne NA, Wienkers LC, Hauer MJ, Sanders PE: Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6. Drug Metab Dispos. 2001 Jan;29(1):41-7. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48