Identification

Name
Delavirdine
Accession Number
DB00705  (APRD00149, DB08563)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Delavirdine mesylate421105KRQE147221-93-0MEPNHSOMXMALDZ-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RescriptorTablet200 mg/1OralKaiser Foundations Hospitals2011-07-062013-06-30Us49702 0210 17 nlmimage10 a618d326
RescriptorTablet100 mgOralViiV Healthcare ULC1998-07-24Not applicableCanada
RescriptorTablet200 mg/1OralViiV Healthcare ULC2012-04-11Not applicableUs
RescriptorTablet200 mg/1OralAgouron Pharmaceuticals1999-11-032015-08-31Us
RescriptorTablet100 mg/1OralViiV Healthcare ULC2010-10-13Not applicableUs49702 0209 24 nlmimage10 131909b8
RescriptorTablet100 mg/1OralAgouron Pharmaceuticals1997-04-182011-04-30Us
RescriptorTablet200 mg/1OralViiV Healthcare Company2010-10-132010-10-13Us
Categories
UNII
DOL5F9JD3E
CAS number
136817-59-9
Weight
Average: 456.561
Monoisotopic: 456.194359482
Chemical Formula
C22H28N6O3S
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

Pharmacology

Indication

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

Associated Conditions
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

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
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.

Affected organisms
  • Human Immunodeficiency Virus
Pathways
PathwayCategory
Delavirdine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Delavirdine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Delavirdine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Delavirdine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Delavirdine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Delavirdine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Delavirdine.
6-Deoxyerythronolide BThe metabolism of Delavirdine can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Delavirdine.
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 without regard to meals.

References

Synthesis Reference
US5563142
General References
Not Available
External Links
Human Metabolome Database
HMDB0014843
KEGG Compound
C06941
PubChem Compound
5625
PubChem Substance
46508878
ChemSpider
5423
BindingDB
1944
ChEBI
119573
ChEMBL
CHEMBL593
Therapeutic Targets Database
DAP000183
PharmGKB
PA449223
HET
SPP
Drugs.com
Drugs.com Drug Page
Wikipedia
Delavirdine
ATC Codes
J05AG02 — Delavirdine
AHFS Codes
  • 08:18.08.16 — Nonnucleoside Reverse Transcriptase Inhibitors
PDB Entries
1klm
FDA label
Download (645 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections5
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
4CompletedNot AvailableInfection, Human Immunodeficiency Virus I1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections6
Not AvailableTerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1

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)
US5563142No1996-10-082013-10-08Us
CA2184598No2005-05-032015-03-01Canada
CA2071529No2001-03-202010-12-24Canada
US6177101No2001-01-232019-06-07Us

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
Polarizability50.01 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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Indolecarboxamide derivative / Indolecarboxylic acid derivative / Pyridinylpiperazine / N-arylpiperazine / Sulfanilide / Indole / Indole or derivatives / 2-heteroaryl carboxamide / Pyrrole-2-carboxamide / Dialkylarylamine
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfonamide, N-carbonylpiperazine, aminopyridine, indolecarboxamide (CHEBI:119573)

Targets

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. [PubMed:16610780]
  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. [PubMed:17656585]
  3. Freimuth WW: Delavirdine mesylate, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor. Adv Exp Med Biol. 1996;394:279-89. [PubMed:8815692]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:19515014]
  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. [PubMed:9765359]
  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. [PubMed:11225565]
  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. [PubMed:11327199]
  5. 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]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. 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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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
Human
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. [PubMed:11225565]
  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. [PubMed:11124228]
  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
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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. [PubMed:11124228]
Kind
Protein
Organism
Human
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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:31