Pleconaril

Pleconaril

Clinical data
Routes of administration	Oral, intranasal
ATC code	J05AX06 (WHO)
Pharmacokinetic data
Bioavailability	70% (oral)
Protein binding	>99%
Metabolism	Hepatic
Excretion	<1% excreted unchanged in urine
Identifiers
IUPAC name 3-{3,5-dimethyl-4-[3-(3-methylisoxazol-5-yl)propoxy] phenyl}-5-(trifluoromethyl)-1,2,4-oxadiazole
CAS Number	153168-05-9 N
PubChem CID	1684
DrugBank	DB05105 N
ChemSpider	1621 Y
UNII	9H4570Q89D
ChEMBL	CHEMBL29609 Y
PDB ligand	W11 (PDBe, RCSB PDB)
ECHA InfoCard	100.208.947
Chemical and physical data
Formula	C18H18F3N3O3
Molar mass	381.35 g/mol
3D model (Jmol)	Interactive image
SMILES FC(F)(F)c1nc(no1)c3cc(c(OCCCc2onc(c2)C)c(c3)C)C
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 Y Key:KQOXLKOJHVFTRN-UHFFFAOYSA-N Y
NY (what is this?)

Pleconaril (Picovir) is an antiviral drug that was being developed by Schering-Plough for prevention of asthma exacerbations and common cold symptoms in patients exposed to picornavirus respiratory infections. Pleconaril, administered either orally or intranasally, is active against viruses in the Picornaviridae family, including Enterovirus and Rhinovirus. It has shown useful activity against the dangerous strain enterovirus D68.

Pleconaril was originally developed by Sanofi-Aventis, and licensed to ViroPharma in 1997. ViroPharma developed it further, and submitted a New Drug Application to the United States Food and Drug Administration (FDA) in 2001. The application was rejected, citing safety concerns; and ViroPharma re-licensed it to Schering-Plough in 2003. The Phase II clinical trial was completed in 2007. A pleconaril intranasal spray had reached phase II clinical trial for the treatment of the common cold symptoms and asthma complications. However, the results have yet to be reported.

In enteroviruses, Pleconaril prevents the virus from exposing its RNA, and in rhinoviruses Pleconaril prevents the virus from attaching itself to the host cell. Human rhinoviruses (HRVs) contain four structural proteins labeled VP1-VP4. Proteins VP1,VP2 and VP3 are eight stranded anti-parallel β-barrels. VP4 is an extended polypeptide chain on the viral capsid inner surface. Pleconaril binds to a hydrophobic pocket in the VP1 protein. Pleconaril has been shown in viral assembly to associate with viral particles. Through noncovalent, hydrophobic interactions compounds can bind to the hydrophobic pocket. Amino acids in positions Tyr152 and Val191 are a part of the VP1 drug binding pocket.