2-Ethoxybenzoxazole as a bioisosteric replacement of an ethyl benzoate group in a human rhinovirus (HRV) capsid binder.
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.
Brown
Renee N
RN
Biota Holdings, 585 Blackburn Road, Notting Hill, VIC-3168, Australia.
Cameron
Rachel
R
Chalmers
David K
DK
Hamilton
Stephanie
S
Luttick
Angela
A
Krippner
Guy Y
GY
McConnell
Darryl B
DB
Nearn
Roland
R
Stanislawski
Pauline C
PC
Tucker
Simon P
SP
Watson
Keith G
KG
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
D001565:Benzoates; D001583:Benzoxazoles; D036022:Capsid Proteins