Pleconaril

Identification

Generic Name

Pleconaril

DrugBank Accession Number

DB05105

Background

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.

Type

Small Molecule

Groups

Investigational

Structure

Similar Structures

Weight: Average: 381.349
Monoisotopic: 381.130026072
Chemical Formula: C₁₈H₁₈F₃N₃O₃

Synonyms

Pleconaril

External IDs

VP 63843
VP63843
WIN 63843

Pharmacology

Indication

Investigated for use/treatment in upper respiratory infection.

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Contraindications & Blackbox Warnings

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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.

Target	Actions	Organism
UPolyprotein	Not Available	Enterovirus 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

Adverse Effects

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Toxicity

Not Available

Pathways

Not Available

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.

Drug	Interaction
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Adenovirus type 7 vaccine live	The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Pleconaril.
Anthrax vaccine	The therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Pleconaril.
Bacillus calmette-guerin substrain connaught live antigen	The therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Pleconaril.
Bacillus calmette-guerin substrain russian BCG-I live antigen	The therapeutic efficacy of Bacillus calmette-guerin substrain russian BCG-I live antigen can be decreased when used in combination with Pleconaril.
Bacillus calmette-guerin substrain tice live antigen	The therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Pleconaril.
BCG vaccine	The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Pleconaril.
Human adenovirus e serotype 4 strain cl-68578 antigen	The therapeutic efficacy of Human adenovirus e serotype 4 strain cl-68578 antigen can be decreased when used in combination with Pleconaril.
Rubella virus vaccine	The therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Pleconaril.
Typhoid Vaccine Live	The therapeutic efficacy of Typhoid Vaccine Live can be decreased when used in combination with Pleconaril.
Varicella zoster vaccine (live/attenuated)	The therapeutic efficacy of Varicella zoster vaccine (live/attenuated) can be decreased when used in combination with Pleconaril.

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Food Interactions

Not Available

Products

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International/Other Brands: Picovir

Chemical Identifiers

UNII: 9H4570Q89D
CAS number: 153168-05-9
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

References

General References

Webster AD: Pleconaril--an advance in the treatment of enteroviral infection in immuno-compromised patients. J Clin Virol. 2005 Jan;32(1):1-6. [Article]
Florea NR, Maglio D, Nicolau DP: Pleconaril, a novel antipicornaviral agent. Pharmacotherapy. 2003 Mar;23(3):339-48. [Article]

External Links

PubChem Compound: 1684
PubChem Substance: 175426946
ChemSpider: 1621
BindingDB: 50111469
ChEMBL: CHEMBL29609
ZINC: ZINC000001537619
PDBe Ligand: W11
Wikipedia: Pleconaril

PDB Entries

1c8m / 1na1 / 1ncq / 1ncr / 1nd3 / 4wm7

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Completed	Prevention	Asthma / Common Cold / Picornavirus Infection / Rhinovirus	1
2	Completed	Treatment	Enteroviral Sepsis	1
2	Completed	Treatment	Enterovirus / Type 1 Diabetes Mellitus	1

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

Property	Value	Source
Water Solubility	0.0219 mg/mL	ALOGPS
logP	4.7	ALOGPS
logP	5.04	ChemAxon
logS	-4.2	ALOGPS
pKa (Strongest Basic)	1.64	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	74.18 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	104.12 m³·mol^-1	ChemAxon
Polarizability	37.46 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9707
Caco-2 permeable	-	0.5395
P-glycoprotein substrate	Non-substrate	0.7624
P-glycoprotein inhibitor I	Non-inhibitor	0.8101
P-glycoprotein inhibitor II	Non-inhibitor	0.727
Renal organic cation transporter	Non-inhibitor	0.9064
CYP450 2C9 substrate	Non-substrate	0.8199
CYP450 2D6 substrate	Non-substrate	0.7861
CYP450 3A4 substrate	Substrate	0.6055
CYP450 1A2 substrate	Inhibitor	0.6447
CYP450 2C9 inhibitor	Non-inhibitor	0.5778
CYP450 2D6 inhibitor	Non-inhibitor	0.8948
CYP450 2C19 inhibitor	Inhibitor	0.7046
CYP450 3A4 inhibitor	Non-inhibitor	0.6775
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.7105
Ames test	Non AMES toxic	0.5384
Carcinogenicity	Non-carcinogens	0.7985
Biodegradation	Not ready biodegradable	0.9923
Rat acute toxicity	2.6286 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9566
hERG inhibition (predictor II)	Non-inhibitor	0.7203

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available