Pleconaril

Identification

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Name
Pleconaril
Accession Number
DB05105  (DB08716)
Type
Small Molecule
Groups
Investigational
Description

Pleconaril is an antiviral drug from viral capsid inhibitor class, manufactured by Schering-Plough and intended for the prevention of acute asthma exacerbations and common cold symptoms in asthmatic patients who have had exposure to picornavirus. It acts by inhibiting viral replication. The use of pleconaril has not gained approval by the U.S. Food and Drug Administration (FDA) due to the fact that it has been found to induce CYP3A enzyme activity, therefore increasing the risk for serious drug interactions.

Structure
Thumb
Synonyms
Not Available
External IDs
VP 63843 / VP63843 / WIN 63843
International/Other Brands
Picovir
Categories
UNII
9H4570Q89D
CAS number
153168-05-9
Weight
Average: 381.349
Monoisotopic: 381.130026072
Chemical Formula
C18H18F3N3O3
InChI Key
KQOXLKOJHVFTRN-UHFFFAOYSA-N
InChI
InChI=1S/C18H18F3N3O3/c1-10-7-13(16-22-17(27-24-16)18(19,20)21)8-11(2)15(10)25-6-4-5-14-9-12(3)23-26-14/h7-9H,4-6H2,1-3H3
IUPAC Name
3-{3,5-dimethyl-4-[3-(3-methyl-1,2-oxazol-5-yl)propoxy]phenyl}-5-(trifluoromethyl)-1,2,4-oxadiazole
SMILES
CC1=NOC(CCCOC2=C(C)C=C(C=C2C)C2=NOC(=N2)C(F)(F)F)=C1

Pharmacology

Indication

Investigated for use/treatment in upper respiratory infection.

Pharmacodynamics
Not Available
Mechanism of action

Pleconaril binds to a hydrophobic pocket in viral protein 1, the major protein which makes up the capsid (shell) of picornaviruses. This renders the viral capsid rigid and compressed and prevents the uncoating of its RNA. As a result, the virus is stopped from attaching to the host cell and causing infection.

TargetActionsOrganism
UPolyproteinNot AvailableEnterovirus J
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

70% (oral)

Volume of distribution
Not Available
Protein binding

>99%

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Adenovirus type 7 vaccine live.
Anthrax vaccineThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Anthrax vaccine.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Bacillus calmette-guerin substrain connaught live antigen.
Bacillus calmette-guerin substrain danish 1331 live antigenThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Bacillus calmette-guerin substrain danish 1331 live antigen.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Bacillus calmette-guerin substrain tice live antigen.
BCG vaccineThe therapeutic efficacy of Pleconaril can be decreased when used in combination with BCG vaccine.
Human adenovirus e serotype 4 strain cl-68578 antigenThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Human adenovirus e serotype 4 strain cl-68578 antigen.
Rubella virus vaccineThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Rubella virus vaccine.
Typhoid Vaccine Live Ty21aThe therapeutic efficacy of Pleconaril can be decreased when used in combination with Typhoid Vaccine Live Ty21a.
Varicella Zoster Vaccine (Live/Attenuated)The therapeutic efficacy of Varicella Zoster Vaccine (Live/Attenuated) can be decreased when used in combination with Pleconaril.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Evidence Level

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Webster AD: Pleconaril--an advance in the treatment of enteroviral infection in immuno-compromised patients. J Clin Virol. 2005 Jan;32(1):1-6. [PubMed:15571999]
  2. Florea NR, Maglio D, Nicolau DP: Pleconaril, a novel antipicornaviral agent. Pharmacotherapy. 2003 Mar;23(3):339-48. [PubMed:12627933]
External Links
PubChem Compound
1684
PubChem Substance
175426946
ChemSpider
1621
BindingDB
50111469
ChEMBL
CHEMBL29609
HET
W11
Wikipedia
Pleconaril
ATC Codes
J05AX06 — Pleconaril
PDB Entries
1c8m / 1na1 / 1ncq / 1ncr / 1nd3 / 4wm7

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionAcute Rhinitis / Asthma Bronchial / Picornavirus Infection / Rhinovirus1
2CompletedTreatmentEnteroviral Sepsis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0219 mg/mLALOGPS
logP4.7ALOGPS
logP5.04ChemAxon
logS-4.2ALOGPS
pKa (Strongest Basic)1.64ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area74.18 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity104.12 m3·mol-1ChemAxon
Polarizability37.46 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9707
Caco-2 permeable-0.5395
P-glycoprotein substrateNon-substrate0.7624
P-glycoprotein inhibitor INon-inhibitor0.8101
P-glycoprotein inhibitor IINon-inhibitor0.727
Renal organic cation transporterNon-inhibitor0.9064
CYP450 2C9 substrateNon-substrate0.8199
CYP450 2D6 substrateNon-substrate0.7861
CYP450 3A4 substrateSubstrate0.6055
CYP450 1A2 substrateInhibitor0.6447
CYP450 2C9 inhibitorNon-inhibitor0.5778
CYP450 2D6 inhibitorNon-inhibitor0.8948
CYP450 2C19 inhibitorInhibitor0.7046
CYP450 3A4 inhibitorNon-inhibitor0.6775
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7105
Ames testNon AMES toxic0.5384
CarcinogenicityNon-carcinogens0.7985
BiodegradationNot ready biodegradable0.9923
Rat acute toxicity2.6286 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9566
hERG inhibition (predictor II)Non-inhibitor0.7203
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 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 phenyloxadiazoles. These are polycyclic aromatic compounds containing a benzene ring linked to a 1,2,4-oxadiazole ring through a CC or CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Oxadiazoles
Direct Parent
Phenyloxadiazoles
Alternative Parents
m-Xylenes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Isoxazoles / Heteroaromatic compounds / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
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Substituents
Phenyl-1,2,4-oxadiazole / Phenoxy compound / Phenol ether / Xylene / M-xylene / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid / Heteroaromatic compound / Isoxazole
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Enterovirus J
Pharmacological action
Unknown
General Function
Structural molecule activity
Specific Function
Not Available
Gene Name
Not Available
Uniprot ID
Q8V397
Uniprot Name
Genome polyprotein
Molecular Weight
241285.765 Da

Drug created on October 21, 2007 16:23 / Updated on May 09, 2019 00:09