Pleconaril

Identification

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

Pleconaril is an antiviral drug being developed by Schering-Plough for prevention of asthma exacerbations and common cold symptoms in asthmatic subjects exposed to picornavirus respiratory infections. Although the formulation used by Schering-Plough is a nasal spray, pleconaril is orally bioavailable, and is active against viruses in the Picornaviridae family, including Enterovirus and Rhinovirus.

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 comprises the capsid (the outer "shell") of picornaviruses. In enteroviruses, this prevents the virus from exposing its RNA, and in rhinoviruses it also prevents the virus from attaching itself to the host cell.

TargetActionsOrganism
UPolyproteinNot AvailableEnterovirus J
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
Influenza a virus a/california/7/2009 (h1n1) live (attenuated) antigenThe therapeutic efficacy of Influenza a virus a/california/7/2009 (h1n1) live (attenuated) antigen can be decreased when used in combination with Pleconaril.
Influenza a virus a/perth/16/2009 (h3n2) live (attenuated) antigenThe therapeutic efficacy of Influenza a virus a/perth/16/2009 (h3n2) live (attenuated) antigen can be decreased when used in combination with Pleconaril.
Influenza Vaccine (Live/Attenuated)The therapeutic efficacy of Pleconaril can be decreased when used in combination with Influenza Vaccine (Live/Attenuated).
Varicella Zoster Vaccine (Live/Attenuated)The therapeutic efficacy of Varicella Zoster Vaccine (Live/Attenuated) can be decreased when used in combination with Pleconaril.
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
show 3 more
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 November 02, 2018 06:08