title: 2-Ethoxybenzoxazole as a bioisosteric replacement of an ethyl benzoate group in a human rhinovirus (HRV) capsid binder.
abstract: A series of pyridazinylpiperidinyl capsid-binding compounds with novel bicyclic substituents were synthesized and screened against human rhinovirus (HRV). Several 2-alkoxy- and 2-alkylthio-benzoxazole and benzothiazole derivatives showed excellent anti-HRV activity. When tested against a panel of 16 representative HRV types the 2-ethoxybenzoxazole derivative 13 was found to have superior HRV activity (median EC(50) 3.88ng/mL) to known capsid-binders Pleconaril and Pirodavir. Compound 13 illustrates that a 2-alkoxybenzoxazole group can be an effective bioisostere for a benzoate ester or benzaldehyde oxime ether functionality.
authors.affiliation: Biota Holdings, 585 Blackburn Road, Notting Hill, VIC-3168, Australia.
authors.forename: Renee N
authors.initials: RN
authors.lastname: Brown
authors.forename: Rachel
authors.initials: R
authors.lastname: Cameron
authors.forename: David K
authors.initials: DK
authors.lastname: Chalmers
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hamilton
authors.forename: Angela
authors.initials: A
authors.lastname: Luttick
authors.forename: Guy Y
authors.initials: GY
authors.lastname: Krippner
authors.forename: Darryl B
authors.initials: DB
authors.lastname: McConnell
authors.forename: Roland
authors.initials: R
authors.lastname: Nearn
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Stanislawski
authors.forename: Simon P
authors.initials: SP
authors.lastname: Tucker
authors.forename: Keith G
authors.initials: KG
authors.lastname: Watson
mesh_terms: D001565:Benzoates / Q000737:chemistry* / Q000378:metabolism; D001583:Benzoxazoles / Q000737:chemistry* / Q000378:metabolism; D036022:Capsid Proteins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D012229:Rhinovirus / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D001565:Benzoates; D001583:Benzoxazoles; D036022:Capsid Proteins